Composition for the dyeing of keratin fibers comprising at least one 3-amino-pyrazolopyridine derivative

ABSTRACT

Disclosed herein is a composition for the dyeing of keratin fibers, for example, human keratin fibers such as the hair, comprising at least one 3-amino pyrazolo-[1,5-a]-pyridine derivative or one of its addition salts and a method employing this derivative. The composition of the present disclosure makes it possible to obtain coloration in various shades that is powerful, chromatic, and aesthetic, with low selectivity and with good resistance to various aggressive factors to which the hair may be subjected, such as shampoos, the light, sweat and permanent shaping.

This is a continuation of application Ser. No. 11/594,967, filed Nov. 9,2006, which issued as U.S. Pat. No. 7,635,394 on Dec. 22, 2009, andwhich claims the benefit of U.S. Provisional Application No. 60/737,462,filed Nov. 17, 2005, and which also claims benefit of priority under 35U.S.C. §119 to French Patent Application No. FR 05 53403, filed Nov. 9,2005, all of which are incorporated herein by reference.

The present disclosure relates to a composition for the dyeing ofkeratin fibers, for example, human keratin fibers such as the hair,comprising at least one 3-aminopyrazolo-[1,5-a]-pyridine derivativeand/or addition salts thereof and a method employing this composition.It also relates to 3-aminopyrazolo-[1,5-a]-pyridine derivatives andaddition salts thereof.

The dyeing of keratin fibers, for example, human keratin fibers such asthe hair, with dyeing compositions comprising oxidation dye precursors,including ortho- or para-phenylenediamines, ortho- or para-aminophenols,and heterocyclic compounds generally called oxidation bases, is known.Oxidation dye precursors, or oxidation bases, are compounds that arecolorless or slightly colored, which, when combined with oxidizingproducts, can give rise to colored or coloring compounds by a process ofoxidative condensation.

It is also known that the shades obtained with these oxidation bases canbe varied by combining them with couplers or dyeing modifiers, thelatter being chosen, for example, from the meta-phenylenediamines, themeta-aminophenols, the meta-hydroxyphenols and certain heterocycliccompounds such as, for example, derivatives ofpyrazolo[1,5-b]-1,2,4-triazoles, derivatives ofpyrazolo[3,2-c]-1,2,4-triazoles, derivatives ofpyrazolo[1,5-a]pyrimidines, derivatives of pyridine, derivatives ofpyrazol-5-one, derivatives of indoline and derivatives of indole.

The variety of molecules employed in the oxidation bases and couplersmeans that a rich palette of colors can be obtained.

The so-called “permanent” dyeing obtained with these oxidation dyesideally, moreover, has at least one of the following advantages: thedyes do not pose any problems in toxicological terms, make it possibleto obtain shades of desired intensity, provide good resistance toexternal factors such as the light, weather, washing, permanent waving,sweating and rubbing, provide coverage of white hair, and/or finallythey have the least possible selectivity, i.e., ensuring the slightestpossible differences in coloration all the way along one and the samekeratin fiber, which may in fact have different sensitivity (i.e. extentof damage) between its tip and its root. The dyes also ideally displaygood chemical stability in the formulations and have a goodtoxicological profile.

The use of oxidation bases such as the derivatives ofpara-phenylenediamine and para-aminophenol may make it possible toobtain quite a wide range of colors at basic pH, though withoutachieving shades with good chromaticity, while endowing the hair with atleast one excellent property chosen from color intensity, variety ofshades, uniformity of color and/or resistance to external factors.

However, the use of these bases at neutral pH is may be ineffective forachieving a range of varied shades, for example, for warm shades.

European Patent Application EP 1 233 743 has already proposed dyecompositions containing 3-amino-pyrazolo-[1,5-a]-pyridines as theoxidation base. However, the dye compositions described in that documentmay not always make it possible to achieve good properties ofchromaticity and/or resistance to external factors such as washing andthe light. Moreover, the range of shades may be of a limited extent.

Thus, it would be desirable to supply novel oxidation bases for thedyeing of keratin fibers which overcome at least one of the drawbacks ofthe existing oxidation bases. For instance, it would be desirable tosupply novel oxidation bases which make it possible to obtain dyeing ina variety of shades that is powerful, chromatic, aesthetic, of lowselectivity, and/or has good resistance to the various aggressivefactors to which the hair may be subjected, such as shampoos, light,sweat and permanent shaping.

The present disclosure, therefore, relates, in at least one embodiment,to dyeing compounds and compositions which make it possible to obtaindyeing having at least one of the above-discussed advantageousproperties. More specifically, the present disclosure relates to acomposition for dyeing keratin fibers comprising, in a medium that issuitable for dyeing, at least one oxidation dyeing base chosen from3-aminopyrazolo-[1,5-a]-pyridine derivatives of the following formula(I) and salts and solvates thereof:

in which

-   -   Z₁ is chosen from an oxygen atom and a group NR₆; when Z₁        represents NR₆, R₁ and R₆ can form, together with the nitrogen        atom to which they are attached, a saturated, unsaturated or        aromatic heterocycle with 5 to 8 ring members, optionally        substituted,

Z₁ can also be a divalent radical chosen from S, SO, and SO₂ when R₁ isa methyl radical,

-   -   R₁ and R₂ are chosen from, independently:        -   a hydrogen atom,        -   C₁-C₁₀ alkyl radicals, optionally substituted, and the            substituent can optionally be a saturated, unsaturated or            aromatic (hetero)cycle with 5 to 8 ring members, optionally            substituted,        -   saturated, unsaturated or aromatic (hetero)cycles with 5 to            8 ring members, optionally substituted,    -   R₃, R₄, and R₅, independently, are chosen from:        -   a hydrogen atom,        -   C₁-C₄ alkyl radicals, optionally substituted,        -   an entity chosen from NH₂, NHR₁₀, NR₁₁R₁₂, OH, and OR₉,            wherein R₉ and R₁₀, which may be identical or different, are            chosen from linear or branched C₁-C₆ alkyl groups,            optionally substituted; R₁₁ and R₁₂, which may be identical            or different, are chosen from linear or branched C₁-C₆ alkyl            groups, optionally substituted; and R₁₁ and R₁₂ can form,            together with the nitrogen atom to which they are attached,            a saturated, unsaturated or aromatic heterocycle with 5 to 8            ring members optionally containing at least one other            heteroatom or group chosen from N, O, S, SO₂, and CO, the            heterocycle being optionally substituted,    -   R₂, R₃, R₄, R₅ can form, two by two with the adjacent radicals,        saturated or unsaturated (hetero)cycles, optionally substituted,        with the exception of 2-methoxypyrazolo[1,5-a]pyridin-3-ylamine        and 2-morpholino-pyrazolo[1,5-a]pyridin-3-ylamine respectively        with the following formulae:

In at least one embodiment, the compositions and compounds of thepresent disclosure make it possible to obtain fast dyeing of keratinfibers, resistant to light and to washing.

Another embodiment relates to a method of dyeing keratin fibersemploying the composition disclosed herein, as well as the use of thiscomposition for the dyeing of keratin fibers.

The present disclosure also relates to novel pyrazolopyridinederivatives of formula (I) except2-methylsulfanyl-pyrazolo[1,5-a]pyridin-3-ylamine and2,3-diamino-pyrazolo[1,5-a]pyridine and their corresponding nitro ornitroso derivatives.

As used herein, “alkyl radical” means linear or branched alkyl radicals,which can be substituted or unsubstituted. They can be substituted withany conventional substituent in the field of dyeing which does not alterthe properties of oxidation base of the compounds of formula (I).

Similarly, when the (hetero)cyclic radicals defined for formula (I) aresubstituted, they can be substituted with any conventional radical inthe field of dyeing which does not alter the properties of oxidationbase of the compounds of formula (I). The following may be mentioned asexamples of substituents of the rings or heterocycles: alkyl radicals,substituted alkyl radicals, hydroxy, alkoxy, amino, alkylamino,dialkylamino, thio, alkylthio, carboxy, alkylcarbonyl, sulphonyl, amidoradicals etc.

The nitrogen-containing heterocycle formed by R₁ and R₆ can contain atleast one other heteroatom, such as a heteroatom selected from N, O, S,SO, SO₂, —CO— and combinations thereof. It can, moreover, be substitutedor unsubstituted, as described above.

The compounds of formula (I) can optionally be salified by strongmineral acids such as HCl, HBr, HI, H₂SO₄, H₃PO₄, or organic acids suchas acetic, lactic, tartaric, citric or succinic, benzenesulphonic,para-toluenesulphonic, formic or methanesulphonic acid.

They can also be in the form of solvates, for example a hydrate or asolvate of a linear or branched alcohol such as ethanol or isopropanol.

As used herein, “derivative of formula (I)” means all mesomeric orisomeric forms.

In formula (I) above, when R₁ and/or R₆ represent a substituted alkylradical, the substituents may, in at least one embodiment, be chosenfrom halogens, and from —OH, —OR₉, —NH₂, —NHR₁₀, —NR₁₁R₁₂, —COR₁₃,—O—CO—R₁₃, —CO—OR₁₄, —NR₁₅—CO—R₁₆, —CO—NR₁₅R₁₆, and —SO₃H radicals, thesaturated or unsaturated cyclic radicals optionally containing aheteroatom chosen from N, S, O, the ring itself possibly beingsubstituted, in which R₉, R₁₀, R₁₁ and R₁₂, which may be identical ordifferent, are as defined previously; R₁₃, R₁₄, R₁₅ and R₁₆, which maybe identical or different, are chosen from hydrogen and C₁-C₆ alkylradicals. In formula (I) above, when R₁ and/or R₆ represent asubstituted alkyl radical, the substituents are also chosen from the—OSO₂R radicals, wherein R is chosen from a linear or branched C₁-C₄alkyl radical and an aromatic radical, optionally substituted. Thefollowing may be mentioned as examples: —OH, —OR₉, —NH₂, —NHR₁₀,—NR₁₁R₁₂, —COR₁₃ radicals, and cyclic radicals such as imidazole,piperazine, pyrrolidine, pyridine, piperidine, morpholine, pyrimidine.

As examples of derivatives of formula (I), the following compounds ortheir addition salts or solvates may be mentioned:

According to at least one embodiment of the present disclosure, theoxidation base of formula (I) above is such that Z₁ is chosen from anoxygen atom, a radical NR₆ and a radical NR₆ forming a heterocycle withR₁.

According to at least one embodiment, the radical R₁ can be chosen froman alkyl radical, an alkyl radical substituted with a hydroxy, an alkylradical substituted with an amino or (di)alkylamino, an alkyl radicalsubstituted with a nitrogen-containing heterocycle, for examplepiperazinyl, imidazolyl, pyrrolidinyl, pyridinyl, morpholinyl, andpiperidinyl. According to one embodiment, the alkyl radical has from 1to 6 carbon atoms.

Radical R₆ can be chosen from a hydrogen atom, an alkyl radical or analkyl radical substituted with a hydroxy radical, an amino radical, analkylamino radical, a dialkyl amino radical, an alkyl radicalsubstituted with a nitrogen-containing heterocycle, for examplepiperazinyl, imidazolyl, pyrrolidinyl, pyridinyl, morpholinyl, andpiperidinyl. According to one embodiment, R₆ has from 1 to 6 carbonatoms.

According to at least one embodiment in which R₁ and R₆ together form aheterocycle with the nitrogen atom to which they are attached, theheterocycle can then be chosen from imidazoles, piperazines,pyrrolidines, and diazapanes, and these heterocycles can be substitutedor unsubstituted.

When R₂, R₃, R₄ and R₅ represent a substituted alkyl radical, this alkylradical can then be substituted, in at least one embodiment, by radicalchosen from —OH, —OR₉, —NH₂, —NHR₁₀, —NR₁₁R₁₂ and SR₉ in which R₉, R₁₀,R₁₁ and R₁₂, which may be identical or different, are as definedpreviously.

Mention may be made, as examples, of methyl, ethyl, hydroxyethyl,aminoethyl, propyl and butyl radicals. According to at least oneembodiment, R₂, R₃, R₄ and R₅ are chosen from, independently, a hydrogenatom and C₁-C₄ alkyl radicals such as methyl, ethyl, propyl, isopropyl,butyl, tert-butyl, or R₄ and R₅ together form a (hetero)cycle with 5 to8 ring members. According to one embodiment, R₄ and R₅ together form asaturated or unsaturated ring with 5 or 8 ring members, such as from 5to 6 ring members, for example a cyclopentane or cyclohexane, optionallysubstituted.

The following compounds may be mentioned as useful herein:

-   N-2-ethylpyrazolo[1,5-a]pyridine-2,3-diamine dihydrochloride,-   2-(3-aminopyrazolo[1,5-a]pyridin-2-ylamino)ethanol dihydrochloride,-   1-(3-aminopyrazolo[1,5-a]pyridin-2-ylamino)propan-2-ol    dihydrochloride,-   N-2-(3-imidazol-1-ylpropyl)pyrazolo[1,5-a]pyridine-2,3-diamine    dihydrochloride,-   2-pyrrolidin-1-ylpyrazolo[1,5-a]pyridin-3-ylamine dihydrochloride,-   2-(3-dimethylaminopyrrolidin-1-yl)pyrazolo[1,5-a]pyridin-3-ylamine    dihydrochloride,-   2-imidazol-1-ylpyrazolo[1,5-a]pyridin-3-ylamine dihydrochloride,-   N-2-(2-pyrrolidin-1-ylethyl)pyrazolo[1,5-a]pyridine-2,3-diamine    dihydrochloride,-   2-(3-aminopyrazolo[1,5-a]pyridin-2-yloxy)ethanol dihydrochloride,-   2-ethoxypyrazolo[1,5-a]pyridin-3-ylamine dihydrochloride,-   2-methoxy-7-methylpyrazolo[1,5-a]pyridin-3-ylamine hydrochloride,-   4-ethyl-2-methoxy-7-methylpyrazolo[1,5-a]pyridin-3-ylamine    dihydrochloride,-   4-ethyl-7-methyl-2-pyrrolidin-1-ylpyrazolo[1,5-a]pyridin-3-ylamine    dihydrochloride,-   N-2-(2-piperidin-1-ylethyl)pyrazolo[1,5-a]pyridine-2,3-diamine    dihydrochloride,-   N-2-2-(diisopropylamino)ethyl]pyrazolo[1,5-a]pyridine-2,3-diamine    dihydrochloride,-   N-2-[2-(diethylamino)ethyl]pyrazolo[1,5-a]pyridine-2,3-diamine    dihydrochloride,-   N-2-(2-pyridin-3-ylethyl)pyrazolo[1,5-a]pyridine-2,3-diamine    dihydrochloride,-   N-2-(2-pyridin-4-ylethyl)pyrazolo[1,5-a]pyridine-2,3-diamine    dihydrochloride,-   N-2-(2-pyridin-2-ylethyl)pyrazolo[1,5-a]pyridine-2,3-diamine    dihydrochloride,-   N-2-(2-piperazin-1-ylethyl)pyrazolo[1,5-a]pyridine-2,3-diamine    dihydrochloride,-   N-2-[2-(4-methylpiperazin-1-yl)ethyl]pyrazolo[1,5-a]pyridine-2,3-diamine    dihydrochloride,-   N-2-(2-morpholin-4-ylethyl)pyrazolo[1,5-a]pyridine-2,3-diamine    dihydrochloride,-   N-2-[2-(dimethylamino)ethyl]-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridine-2,3-diamine    dihydrochloride,-   2-[(3-amino-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridin-2-yl)amino]ethanol    hydrochloride,-   2-methoxy-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridin-3-amine    hydrochloride,-   2-isopropoxy-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridin-3-amine    hydrochloride,-   2-[2-(dimethylamino)ethoxy]pyrazolo[1,5-a]pyridin-3-amine    dihydrochloride,-   2-(2-pyrrolidin-1-ylethoxy)pyrazolo[1,5-a]pyridin-3-amine    dihydrochloride,-   2-(2-piperidin-1-ylethoxy)pyrazolo[1,5-a]pyridin-3-amine    dihydrochloride,-   2-(2-morpholin-4-ylethoxy)pyrazolo[1,5-a]pyridin-3-amine    dihydrochloride,-   2-[2-(diisopropylamino)ethoxy]pyrazolo[1,5-a]pyridin-3-amine    dihydrochloride,-   2-(2-pyridin-2-ylethoxy)pyrazolo[1,5-a]pyridin-3-amine    dihydrochloride,-   2-(2-pyridin-3-ylethoxy)pyrazolo[1,5-a]pyridin-3-amine    dihydrochloride,-   2-(2-pyridin-4-ylethoxy)pyrazolo[1,5-a]pyridin-3-amine    dihydrochloride,-   N-5,N-5-dimethyl-2-methylsulphanylpyrazolo[1,5-a]pyridine-3,5-diamine    dihydrochloride.

The at least one oxidation base is present (for each base) in an amountranging from 0.001 to 10 wt. % of the total weight of the dyeingcomposition, such as from 0.005 to 6%.

The dyeing composition of the present disclosure may comprise at leastone coupler conventionally used for the dyeing of keratin fibers. Amongthese couplers, mention may be made, for example, ofmeta-phenylenediamines, meta-aminophenols, meta-diphenols, naphthaleniccouplers, heterocyclic couplers and their addition salts.

The following examples may be mentioned: 2-methyl-5-aminophenol,5-N-(β-hydroxyethyl)amino-2-methylphenol,6-chloro-2-methyl-5-aminophenol, 3-aminophenol, 1,3-dihydroxybenzene,1,3-dihydroxy-2-methylbenzene, 4-chloro-1,3-dihydroxybenzene,2,4-diamino-1-(β-hydroxyethyloxy)benzene,2-amino-4-(β-hydroxyethylamino)-1-methoxybenzene, 1,3-diaminobenzene,1,3-bis-2,4-diaminophenoxy)propane, 3-ureido-aniline,3-ureido-1-dimethylaminobenzene, sesamol,1-β-hydroxyethylamino-3,4-methylenedioxybenzene, α-naphthol,2-methyl-1-naphthol, 6-hydroxyindole, 4-hydroxyindole,4-hydroxy-N-methyl indole, 2-amino-3-hydroxypyridine,6-hydroxy-benzomorpholine, 3,5-diamino-2,6-dimethoxypyridine,1-N-(β-hydroxyethyl)amino-3,4-methylene dioxybenzene,2,6-bis-(β-hydroxyethylamino)toluene and their acid-addition salts.

In the composition of the present disclosure, the at least one coupleris present (for each coupler) in an amount ranging from 0.001 to 10 wt.% of the total weight of the dyeing composition, such as from 0.005 to6%.

The composition of the present disclosure can, in addition, comprise atleast one additional oxidation base conventionally used in oxidationdyeing other than those described previously. For example, theseadditional oxidation bases may be chosen from para-phenylenediamines,bis-phenylalkylenediamines, para-aminophenols, bis-para-aminophenols,ortho-aminophenols, ortho-phenylenediamines, heterocyclic basesdifferent from the derivatives of formula (I) as defined previously andtheir addition salts.

Among the para-phenylenediamines, the following may be mentioned asexamples: para-phenylenediamine, para-toluoylenediamine,2-chloro-para-phenylenediamine, 2,3-dimethyl para-phenylenediamine,2,6-dimethyl para-phenylenediamine, 2,6-diethyl para-phenylenediamine,2,5-dimethyl para-phenylenediamine, N,N-dimethyl para-phenylenediamine,N,N-diethyl para-phenylenediamine, N,N-dipropyl para-phenylenediamine,4-amino N,N-diethyl 3-methylaniline,N,N-bis-(β-hydroxyethyl)para-phenylenediamine,4-N,N-bis-(β-hydroxyethyl)amino 2-methylaniline,4-N,N-bis-(β-hydroxyethyl)amino 2-chloro aniline, 2-(β-hydroxyethylpara-phenylenediamine, 2-fluoro para-phenylenediamine, 2-isopropylpara-phenylenediamine, N-(β-hydroxypropyl)para-phenylenediamine,2-hydroxymethyl para-phenylenediamine, N,N-dimethyl 3-methylpara-phenylenediamine, N,N-(ethyl, β-hydroxyethyl)para-phenylenediamine,N-(β,γ-dihydroxypropyl)para-phenylenediamine,N-(4′-aminophenyl)para-phenylenediamine, N-phenyl para-phenylenediamine,2-(β-hydroxyethyloxy para-phenylenediamine, 2-β-acetylaminoethyloxypara-phenylenediamine, N-(β-methoxyethyl)para-phenylenediamine4-aminophenylpyrrolidine, 2-thienyl para-phenylenediamine, 2-βhydroxyethylamino-5-amino toluene, 3-hydroxy1-(4′-aminophenyl)pyrrolidine and their acid-addition salts.

Among the para-phenylenediamines mentioned above, further mention may bemade of: para-phenylenediamine, para-toluoylenediamine, 2-isopropylpara-phenylenediamine, 2-β-hydroxyethyl para-phenylenediamine,2-β-hydroxyethyloxy para-phenylenediamine, 2,6-dimethylpara-phenylenediamine, 2,6-diethyl para-phenylenediamine, 2,3-dimethylpara-phenylenediamine, N,N-bis-(β-hydroxyethyl)para-phenylenediamine,2-chloro para-phenylenediamine, 2-β-acetylaminoethyloxypara-phenylenediamine, and their acid-addition salts.

The following may be mentioned as examples of thebis-phenylalkylenediamines:N,N′-bis-(β-hydroxyethyl)N,N′-bis-(4′-aminophenyl) 1,3-diaminopropanol,N,N′-bis-(β-hydroxyethyl)N,N′-bis-(4′-aminophenyl)ethylenediamine,N,N′-bis-(4-aminophenyl)tetramethylenedimine,N,N′-bis-(β-hydroxyethyl)N,N′-bis-(4-aminophenyl)tetramethylenediamine,N,N′-bis-(4-methyl-aminophenyl)tetramethylenediamine,N,N′-bis-(ethyl)N,N′-bis-(4′-amino 3′-methylphenyl)ethylenediamine,1,8-bis-(2,5-diaminophenoxy)-3,6-dioxaoctane, and their acid-additionsalts.

The following may be mentioned as examples of the para-aminophenols:para-aminophenol, 4-amino 3-methylphenol, 4-amino 3-fluorophenol,4-amino 3-hydroxymethylphenol, 4-amino 2-methylphenol, 4-amino2-hydroxymethylphenol, 4-amino 2-methoxymethylphenol, 4-amino2-aminomethylphenol, 4-amino 2-(β-hydroxyethyl aminomethyl)phenol,4-amino 2-fluorophenol, and their acid-addition salts.

The following may be mentioned as examples of the ortho-aminophenols:2-aminophenol, 2-amino 5-methylphenol, 2-amino 6-methylphenol,5-acetamido 2-aminophenol, and their acid-addition salts.

The following may be mentioned as examples of the heterocyclic bases:pyridine derivatives, pyrimidine derivatives and pyrazole derivatives.

Among the pyridine derivatives, the following compounds may bementioned: the compounds described, for example, in British Patents GB 1026 978 and GB 1 153 196, as well as 2,5-diaminopyridine,2-(4-methoxyphenyl)amino 3-aminopyridine, 2,3-diamino-6-methoxypyridine,2-(β-methoxyethyl)amino 3-amino-6-methoxypyridine, 3,4-diaminopyridine,and their acid-addition salts.

Other pyridine oxidation bases that can be used herein are the3-amino-pyrazolo-[1,5-a]-pyridine oxidation bases or their additionsalts described, for example, French Patent Application FR 2 801 308.The following may be mentioned as examples:pyrazolo[1,5-a]pyridin-3-ylamine; 2-acetylaminopyrazolo[1,5-a]pyridin-3-ylamine;2-morpholin-4-yl-pyrazolo[1,5-a]pyridin-3-ylamine;3-amino-pyrazolo[1,5-a]pyridin-2-carboxylic acid;2-methoxy-pyrazolo[1,5-a]pyridin-3-ylamino;(3-amino-pyrazolo[1,5-a]pyridin-7-yl)-methanol;2-(3-amino-pyrazolo[1,5-a]pyridin-5-yl)-ethanol;2-(3-amino-pyrazolo[1,5-a]pyridin-7-yl)-ethanol;(3-amino-pyrazolo[1,5-a]pyridin-2-yl)-methanol;3,6-diamino-pyrazolo[1,5-a]pyridine;3,4-diamino-pyrazolo[1,5-a]pyridine;pyrazolo[1,5-a]pyridine-3,7-diamine;7-morpholin-4-yl-pyrazolo[1,5-a]pyridin-3-ylamine;pyrazolo[1,5-a]pyridine-3,5-diamine;5-morpholin-4-yl-pyrazolo[1,5-a]pyridin-3-ylamine;2-[(3-amino-pyrazolo[1,5-a]pyridin-5-yl)-(2-hydroxyethyl)-amino]-ethanol;2-[(3-amino-pyrazolo[1,5-a]pyridin-7-yl)-(2-hydroxyethyl)-amino]-ethanol;3-amino-pyrazolo[1,5-a]pyridin-5-ol;3-amino-pyrazolo[1,5-a]pyridin-4-ol;3-amino-pyrazolo[1,5-a]pyridin-6-ol;3-amino-pyrazolo[1,5-a]pyridin-7-ol; as well as their addition saltswith an acid or with a base.

Among the pyrimidine derivatives, mention may be made of the compoundsdescribed, for example, in patents DE 23 59 399; JP 88-169571; JP05-163124; EP 0 770 375 or published patent application WO 96/15765 suchas 2,4,5,6-tetra-aminopyrimidine, 4-hydroxy 2,5,6-triaminopyrimidine,2-hydroxy 4,5,6-triaminopyrimidine, 2,4-dihydroxy 5,6-diaminopyrimidine,2,5,6-triaminopyrimidine, and the pyrazolo-pyrimidine derivatives suchas those mentioned in French Patent Application FR-A-2 750 048 and amongwhich we may mention pyrazolo-[1,5-a]-pyrimidine-3,7-diamine,2,5-dimethylpyrazolo-[1,5-a]-pyrimidine-3,7-diamine;pyrazolo-[1,5-a]-pyrimidine-3,5-diamine;2,7-dimethylpyrazolo-[1,5-a]-pyrimidine-3,5-diamine; 3-aminopyrazolo-[1,5-a]-pyrimidin-7-ol; 3-aminopyrazolo-[1,5-a]-pyrimidin-5-ol; 2-(3-aminopyrazole-[1,5-a]-pyrimidin-7-ylamino)-ethanol, 2-(7-aminopyrazolo-[1,5-a]-pyrimidin-3-ylamino)-ethanol,2-[(3-amino-pyrazolo-[1,5-a]-pyrimidin-7-yl)-(2-hydroxy-ethyl)-amino]-ethanol,2-[(7-amino-pyrazolo-[1,5-a]-pyrimidin-3-yl)-(2-hydroxy-ethyl)-amino]-ethanol,5,6-dimethylpyrazolo-[1,5-a]-pyrimidine-3,7-diamine, 2,6-dimethylpyrazolo-[1,5-a]-pyrimidine-3,7-diamine, 2,5,N7,N7-tetramethylpyrazolo-[1,5-a]-pyrimidine-3,7-diamine,3-amino-5-methyl-7-imidazolylpropylamino pyrazolo-[1,5-a]-pyrimidine andtheir acid-addition salts and their tautomeric forms, when a tautomericequilibrium exists.

Among the pyrazole derivatives, mention may be made of the compoundsdescribed in patents DE 38 43 892, DE 41 33 957 and patent applicationsWO 94/08969, WO 94/08970, FR-A-2 733 749 and DE 195 43 98,8 such as4,5-diamino 1-methylpyrazole, 4,5-diamino 1-(β-hydroxyethyl)pyrazole,3,4-diamino pyrazole, 4,5-diamino 1-(4′-chlorobenzyl)pyrazole,4,5-diamino 1,3-dimethylpyrazole, 4,5-diamino 3-methyl 1-phenylpyrazole, 4,5-diamino 1-methyl 3-phenyl pyrazole, 4-amino 1,3-dimethyl5-hydrazino pyrazole, 1-benzyl 4,5-diamino 3-methylpyrazole, 4,5-diamino3-tert-butyl 1-methyl pyrazole, 4,5-diamino 1-tert-butyl3-methylpyrazole, 4,5-diamino 1-(β-hydroxyethyl) 3-methylpyrazole,4,5-diamino 1-ethyl 3-methylpyrazole, 4,5-diamino 1-ethyl3-(4′-methoxyphenyl)pyrazole, 4,5-diamino 1-ethyl3-hydroxymethylpyrazole, 4,5-diamino 3-hydroxymethyl 1-methylpyrazole,4,5-diamino 3-hydroxymethyl 1-isopropyl pyrazole, 4,5-diamino 3-methyl1-isopropyl pyrazole, 4-amino 5-(2′-aminoethyl)amino 1,3-dimethylpyrazole, 3,4,5-triamino pyrazole, 1-methyl 3,4,5-triamino pyrazole,3,5-diamino 1-methyl 4-methylamino pyrazole, 3,5-diamino4-(β-hydroxyethyl)amino 1-methylpyrazole, and their acid-addition salts.

The at least one additional oxidation base other than those of formula(I) present in the composition of the disclosure is present (for each)in an amount ranging from 0.001 to 10 wt. % of the total weight of thedyeing composition, such as from 0.005 to 6%.

In at least one embodiment, the addition salts of these additionaloxidation bases and of the couplers that can be used within the scope ofthe present disclosure may be chosen from acid-addition salts such asthe hydrochlorides, hydrobromides, sulphates, citrates, succinates,tartrates, lactates, tosylates, benzenesulphonates, phosphates andacetates and base-addition salts such as sodium hydroxide, potassiumhydroxide, ammonia, amines or alkanolamines.

The dyeing composition according to the present disclosure canadditionally comprise at least one direct dye which can, in at least oneembodiment, be chosen from the nitro dyes of the benzene series, the azodirect dyes and the methine direct dyes. These direct dyes can be of anon-ionic, anionic or cationic nature.

As defined herein, the suitable medium for dyeing, also called thedyeing support, is a cosmetic medium comprising water or a mixture ofwater and at least one organic solvent for dissolving the compounds thatwould not be sufficiently soluble in water. Examples of such organicsolvents include, for example, the C₁-C₄ lower alkanols, such as ethanoland isopropanol; polyols and polyol ethers such as 2-butoxyethanol,propylene glycol, monomethyl ether of propylene glycol, the monoethylether and monomethyl ether of diethylene glycol, as well as the aromaticalcohols such as benzyl alcohol or phenoxyethanol, and mixtures thereof.

In at least one embodiment, the solvents are present in an amountranging from 1 to 40 wt. % relative to the total weight of the dyeingcomposition, such as from 5 to 30 wt. %.

The dyeing composition according to the present disclosure may alsocomprise at least one additive conventionally used in compositions fordyeing the hair, such as anionic, cationic, non-ionic, amphoteric,zwitterionic surfactants or mixtures thereof, anionic, cationic,non-ionic, amphoteric, zwitterionic polymers or mixtures thereof,inorganic or organic thickeners, such as anionic, cationic, non-ionicand amphoteric associative polymeric thickeners, antioxidants,penetrants, sequestering agents, perfumes, buffers, dispersants,conditioning agents such as volatile or non-volatile, modified orunmodified silicones, film-forming agents, ceramides, preservatives, andopacifiers.

When present, the at least one additive is present, in an amount foreach of them, ranging from 0.01 to 20 wt. % relative to the weight ofthe dyeing composition.

A person skilled in the art will of course make sure that any additionalcompound or compounds are chosen in such a way that the advantageousproperties intrinsic to the oxidation dyeing composition according tothe present disclosure are not, or substantially not, affected adverselyby the addition or additions envisaged.

The pH of the presently disclosed dyeing composition ranges from 3 to12, such as from 5 to 11. It can be adjusted to the desired value bymeans of acidifying or alkalizing agents usually employed in the dyeingof keratin fibers or alternatively by means of conventional bufferingsystems.

Among the acidifying agents, the following may be mentioned as examples:mineral or organic acids such as hydrochloric acid, orthophosphoricacid, sulphuric acid, carboxylic acids such as acetic acid, tartaricacid, citric acid, lactic acid, and sulphonic acids.

Among the alkalizing agents, the following may be mentioned as examples:ammonia, alkali metal carbonates, alkanolamines such as the mono-, di-and tri-ethanolamines as well as their derivatives, the hydroxides ofsodium or potassium and the compounds of the following formula (II):

in which W is a propylene residue optionally substituted with a hydroxylgroup or a C₁-C₄ alkyl radical; R_(a), R_(b), R_(c) and R_(d), which maybe identical or different, are each chosen from a hydrogen atom, C₁-C₄alkyl radicals and C₁-C₄ hydroxyalkyl radicals.

The dyeing composition according to the present disclosure can be invarious forms, such as in the form of liquids, creams, gels, or in anyother form that is suitable for carrying out dyeing of keratin fibers,such as human hair.

The method of the present disclosure is a method in which thecomposition according to the present disclosure as defined previously isapplied to the fibers, and the color is developed by means of anoxidizing agent. The color can be developed at acid, neutral or alkalinepH and the oxidizing agent can be added to the composition right at themoment of use or it can be used on the basis of an oxidizing compositioncontaining it, applied simultaneously with or sequentially to thecomposition of the disclosure.

According to at least one embodiment, the composition according to thepresent disclosure is mixed, for example at the moment of use, with acomposition containing, in a medium suitable for dyeing, at least oneoxidizing agent, said oxidizing agent being present in an amountsufficient for developing a coloration. The mixture obtained is thenapplied to the keratin fibers. After a waiting time of 3 to 50 minutes,such as from 5 to 30 minutes, the keratin fibers are rinsed, washed withshampoo, rinsed again and then dried.

The oxidizing agents conventionally used for the oxidation dyeing ofkeratin fibers are, for example, hydrogen peroxide, urea peroxide,alkali metal bromates, per-salts such as perborates and persulphates,peracids and the oxidase enzymes, such as peroxidases, 2-electronoxidoreductases such as uricases and 4-electron oxygenases such aslaccases. In one embodiment, hydrogen peroxide is used.

The oxidizing composition can also comprise at least one additive usedconventionally in compositions for dyeing the hair and as definedpreviously.

The pH of the oxidizing composition containing the oxidizing agent issuch that after mixing with the dyeing composition, the pH of theresultant composition applied to the keratin fibers ranges, in at leastone embodiment, from 3 to 12, such as from 5 to 11. It can be adjustedto the desired value by means of acidifying or alkalizing agents usuallyemployed in the dyeing of keratin fibers and as defined previously.

The ready-to-use composition which is finally applied to the keratinfibers can be in various forms, such as in the form of liquids, creams,gels or in any other form suitable for carrying out dyeing of keratinfibers, such as human hair.

The present disclosure also relates to a dyeing “kit” with severalcompartments, in which a first compartment contains the dyeingcomposition of the present disclosure defined above and a secondcompartment contains an oxidizing composition. This kit can be equippedwith a means for delivering the desired mixture onto the hair, such asthe kits described in French Patent FR-2 586 913.

Using this kit, it is possible to dye keratin fibers by a method thatcomprises mixing a dyeing composition containing at least one oxidationbase of formula (I) with an oxidizing agent, and applying the mixtureobtained on the keratin fibers for a time that is sufficient to developthe desired coloration.

The present disclosure also relates to the use of a pyrazolopyridinederivative of formula (I) or of one of its addition salts as previouslydefined for the oxidation dyeing of keratin fibers, for example, ofhuman keratin fibers such as the hair.

The compounds of formula (I) that can be used in the present disclosurecan be obtained from intermediates and by synthetic routes described inthe literature, such as in the following references: J. Het. Chem.,2001, 38(3), 613-616; Helvetica Chimica Acta, 1950, 33, 1183-1194; J.Org. Chem., 23, 2029 (1958); J. Am. Chem. Soc., 73, 3240 (1951); J. Am.Chem. Soc., 84, 590 (1962); Justus Liebig Ann. Chem., 686, 134 (1965);Tetrahedron Lett., 31, 2859-2862 (1973), U.S. Pat. Nos. 4,128,425 and2,841,584 and the references cited therein.

According to at least one embodiment, the compounds of formula (I) canbe synthesized according to the following scheme:

in which R′₂, R′₃, R′₄ and R′₅ have the same meanings as R₂, R₃, R₄ andR₅ or are precursors thereof.

As an example, when R₁ is an alkyl radical (C₁-C₁₀)—NR₁₁R₁₂ or an alkylradical (C₁-C₁₀)—OR₁₁, the following method of synthesis can be used:

Further details of these routes of synthesis are given in the examplesdescribed below.

The present disclosure also relates to the intermediates (A) and (B) asdefined above in which at least one of the radicals R′₂, R′₃, R′₄ or R′₅is different from a hydrogen atom apart from the compound for whichR′₂=Me when all the other substituents are hydrogen.

The present disclosure also relates to intermediates of formula (C),(D), (F), (H), (I) as defined above.

Other than in the examples, or where otherwise indicated, all numbersexpressing quantities of ingredients, reaction conditions, and so forthused in the specification and claims are to be understood as beingmodified in all instances by the term “about.” Accordingly, unlessindicated to the contrary, the numerical parameters set forth in thespecification and attached claims are approximations that may varydepending upon the desired properties sought to be obtained by thepresent disclosure. At the very least, and not as an attempt to limitthe application of the doctrine of equivalents to the scope of theclaims, each numerical parameter should be construed in light of thenumber of significant digits and ordinary rounding approaches.

Notwithstanding that the numerical ranges and parameters setting forththe broad scope of the disclosure are approximations, unless otherwiseindicated the numerical values set forth in the specific examples arereported as precisely as possible. Any numerical value, however,inherently contain certain errors necessarily resulting from thestandard deviation found in their respective testing measurements.

By way of non-limiting illustration, concrete examples of certainembodiments of the present disclosure are given below. In the texthereinbelow, “A.M.” means Active Material.

EXAMPLES Example 1 N-2-Ethyl pyrazolo[1,5-a]pyridine-2,3-diaminedihydrochloride

Synthesis of 2-methylsulphanyl-3-nitro-pyrazolo[1,5-a]pyridine

A solution of 111 g of 1-N-aminopyridinium iodide (0.5 mol) in DMF (500ml) was prepared in a 2-liter three-necked flask equipped with amechanical stirrer and an internal temperature sensor under a stream ofnitrogen.

Potassium carbonate (207.3, 3 eq.) was then added in one go, followed by1,1-bis(methylthio)-2-nitroethylene (165.2 g, 2 eq.), also in one go.The weight of the reaction mixture increased. Then 500 ml of DMF wereadded to make the reaction mixture more fluid.

After being stirred for 48 h at room temperature, the reaction mixturewas poured into 4 liters of ice water. The precipitate that formed wasfiltered and washed with plenty of water (5 liters), then dried at 80°C. under vacuum.

The excess 1,1-bis(methylthio)-2-nitroethylene (30 mol. % determined by¹H-NMR) was removed from the solid thus obtained by re-pasting in ethylacetate. After draining and drying, 72 g of a yellowish-beige solid,corresponding to the expected product, was obtained.

¹H-NMR (300 MHz, DMSO-d₆):

8.98 (1H, d); 8.20 (1H, d), 7.89 (1H, m), 7.36 (1H, m), 2.63 (3H, s).

Synthesis of 2-methanesulphonyl-3-nitro-pyrazolo[1,5-a]pyridine

In succession, 880 g of Oxone (5 eq.), 2 liters of water and 60 g of2-methylsulphonyl-3-nitro-pyrazolo[1,5-a]pyridine (0.287 eq.) obtainedpreviously, were put in a 4-liter three-necked flask equipped with amechanical stirrer and an internal temperature sensor. The whole wasstirred at room temperature.

The reaction was completed by adding Oxone (120 g, 0.7 eq.), and after 4h stirring at room temperature, the reaction was stopped.

The solid that formed was drained and washed with plenty of water untila filtrate was obtained that no longer contained peroxide. The filtratewas then placed under vacuum at 40° C. over P₂O₅.

59 g of the expected product was obtained in the form of ayellowish-beige powder.

¹H-NMR (300 MHz, DMSO-d₆):

9.15 (1H, d); 8.35 (1H, d), 8.03 (1H, m), 7.56 (1H, m), 3.59 (3H, s).

Synthesis of ethyl-(3-nitro-pyrazolo[1,5-a]pyridin-2-yl)-amine

3 ml of N-methypyrrolidinone, 2.41 g (0.01 mol)2-methanesulphonyl-3-nitro-pyrazolo[1,5-a]pyridine and 4.015 g ofethylamine were put in a 10-ml three-necked flask equipped with a bulbcondenser, a thermometer and a magnetic stirrer. While stirring, themixture was heated to 70° C. on an oil bath, for 5 hours.

The yellow compound isolated by pouring the reaction mixture into waterwas drained on a frit and then washed with water several times. Afterdrying under vacuum, in the presence of P₂O₅, 1.68 g of a yellow solidwere recovered, corresponding to the expected compound.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure. The mass of the expected compound C₉H₁₀N₄O₂was detected in mass spectrometry. The quasi-molecular ions [M+H]⁺,[M+Na]⁺ and [M−H]⁻ of the expected molecule, C₉H₁₀N₄O₂, were mainlydetected.

Synthesis of N-2-ethyl pyrazolo[1,5-a]pyridine-2,3-diaminedihydrochloride

400 ml of ethanol and 11 g of zinc powder were put in a 500-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and brought to reflux.

2.25 g of ammonium chloride dissolved in 0.5 ml of water were thenadded, and 3 g of ethyl-(3-nitro-pyrazolo[1,5-a]pyridin-2-yl)-amine wasadded in portions over a period of 15 minutes. Reflux was maintained for2 hours.

When reduction ended, the zinc was removed by filtration under argon ona bed of Celite and the filtrate was collected in a flask containing 50ml of previously cooled 6N hydrochloric isopropanol. The zinc was washedwith ethanol, the filtrates were combined and evaporated to dryness.

After vacuum drying, in the presence of P₂O₅ and soda tablets, 2.1 g ofa blue powder corresponding to the expected compound was obtained.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure. The quasi-molecular ions [M+H]⁺ and [M+Na]⁺of the expected molecule were detected: C₉H₁₂N₄.

Example 2 2-(3-Amino-pyrazolo[1,5-a]pyridin-2-ylamino)-ethanoldihydrochloride

Synthesis of 2-[3-nitro pyraxolo[1,5-a]pyridin-2-yl)amino]ethanol

10 ml of N-methypyrrolidinone, 7.25 g (0.03 mol)2-methanesulphonyl-3-nitro-pyrazolo[1,5-a]pyridine and 6 ml ethanolaminewere put in a 50-ml three-necked flask equipped with a bulb condenser, athermometer and a magnetic stirrer. While being stirred, the mixture washeated to 70° C. on an oil bath for 5 hours.

The yellow compound, isolated by pouring the reaction mixture intowater, was drained on a frit and then washed with water several times.After drying under vacuum, in the presence of P₂O₅, 6.45 g of yellowsolid corresponding to the expected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure.

The quasi-molecular ions [M+H]⁺, [M+Na]⁺ and [M−H]⁻ of the expectedmolecule, C₉H₁₀N₄O₃, were mainly detected.

Synthesis of 2-(3-amino-pyrazolo[1,5-a]pyridin-2-ylamino)-ethanoldihydrochloride

350 ml of ethanol and 5 g of zinc powder were put in a 500-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and brought to reflux.

1 g of ammonium chloride dissolved in 0.5 ml water was then added, and 2g of 2-[(3-nitro pyrazolo[1,5-a]pyridin-2-yl)amino]ethanol were added inportions over a period of 15 minutes. Reflux was maintained for 4 h.

At the end of reduction, the zinc was removed by filtration under argonon a bed of Celite and the filtrate collected in a flask containing 50ml of previously cooled 6N hydrochloric isopropanol. The zinc was washedwith ethanol, the filtrates were combined and evaporated to dryness.

After being dried under vacuum, in the presence of P₂O₅ and sodatablets, 1.23 g of a bluish powder corresponding to the expectedcompound was obtained.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure.

The quasi-molecular ions [M+H]⁺, [M+Na]⁺ and [M−H]⁻ of the expectedmolecule, C₉H₁₂N₄O, were mainly detected.

Example 3 1-(3-Amino-pyrazolo[1,5-a]pyridin-2-ylamino)-propan-2-ol

Synthesis of 1-[(3-nitro pyrazolo[1,5-a]pyridin-2-yl)amino]propan-2-ol

10 ml of N-methypyrrolidinone, 7.23 g (0.03 mol)2-methanesulphonyl-3-nitro-pyrazolo[1,5-a]pyridine and 7 ml of1-amino-2-propanol were put in a 50-ml three-necked flask equipped witha bulb condenser, a thermometer and a magnetic stirrer. While beingstirred, the mixture was heated to 70° C. on an oil bath, for 5 hours.

The yellow compound, isolated by pouring the reaction mixture intowater, was drained on a frit and then washed with water several times.After drying under vacuum, in the presence of P₂O₅, 6.02 g of a yellowsolid corresponding to the expected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure.

Synthesis of 1-(3-amino-pyrazolo[1,5-a]pyridin-2-ylamino)-propan-2-oldihydrochloride

350 ml of ethanol and 5 g of zinc powder were put in a 500-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and brought to reflux.

Then 1 g of ammonium chloride dissolved in 0.5 ml water was added, and 2g of 1-[(3-nitropyrazolo[1,5-a]pyridin-2-yl)amino]propan-2-ol was addedin portions over a period of 15 minutes. Reflux was maintained for 4hours.

At the end of reduction, the zinc was removed by filtration under argonon a bed of Celite and the filtrate was collected in a flask containing50 ml of previously cooled 6N hydrochloric isopropanol, the zinc waswashed with ethanol, the filtrates were combined and evaporated todryness.

After drying under vacuum, in the presence of P₂O₅ and soda tablets, 1.5g of a bluish powder corresponding to the expected compound wasobtained.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure. The quasi-molecular ions [M+H]⁺ and [M+Na]⁺of the expected molecule, C₁₀H₁₄N₄O, were mainly detected.

Example 4N-2-(3-Imidazol-1-yl-propyl)pyrazolo[1,5-a]pyridine-2,3-diaminedihydrochloride

Synthesis ofN-[3-(1H-imidazol-1-yl)propyl]-3-nitropyrazolo[1,5-a]pyridin-2-amine

50 ml of N-methypyrrolidinone, 5 g (0.021 mol) of2-methanesulphanyl-3-nitropyrazolo[1,5-a]pyridine and 26 g of3-(1H-imidazol-1-yl)propane-1-amine were put in a 100-ml three-neckedflask equipped with a bulb condenser, a thermometer and a magneticstirrer and stirring was continued for 6 hours, monitoring by TLC(eluent: 95:5 dichloromethane/methanol).

The reaction medium was poured onto a mixture of 200 g of ice and water.The yellow compound that crystallized was drained on a No. 3 frit,washed with water 2×100 ml then with 3×100 ml of isopropyl ether. Afterdrying at 35° C. under vacuum, in the presence of P₂O₅, for 12 hours, 5g of a green solid corresponding to the expected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrophotometry were consistent with the expected structure. Thequasi-molecular ions [M+H]⁺, [2M+H]⁺ of the expected molecule,C₁₃H₁₄N₆O₂, were mainly detected.

Synthesis ofN-2-(3-imidazol-1-yl-propyl)-pyrazolo[1,5-a]pyridine-2,3-aminedihydrochloride

350 ml of ethanol and 5 g of zinc powder were put in a 500-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and brought to reflux.

Then 1 g of ammonium chloride dissolved in 0.5 ml water was added, and 1g ofN-[3-(1H-imidazol-1-yl)propyl]-3-nitropyrazolo[1,5-a]pyridin-2-amine wasadded in portions in 15 minutes. Reflux was maintained for 4 hours.

At the end of reduction, the zinc was removed by filtration under argonon a bed of Celite and the filtrate was collected in a flask containing50 ml of previously cooled 6N hydrochloric isopropanol. The zinc waswashed with ethanol, the filtrates were combined and evaporated todryness.

After drying under vacuum, in the presence of P₂O₅ and soda tablets, 0.5g of a bluish powder corresponding to the expected compound wasobtained. The quasi-molecular ions [M+H]⁺, [M+Na]⁺ of the expectedmolecule, C₁₃H₁₆N₆, were mainly detected.

Example 5 2-Pyrrolidin-1-yl-pyrazolo[1,5-a]pyridin-3-ylaminedihydrochloride

Synthesis of 3-nitro-2-pyrrolidin-1-yl-pyrazolo[1,5-a]pyridine

10 ml of N-methypyrrolidinone, 7.23 g (0.03 mol)2-methanesulphonyl-3-nitro-pyrazolo[1,5-a]pyridine and 8 ml pyrrolidinewere put in a 50-ml three-necked flask equipped with a bulb condenser, athermometer and a magnetic stirrer. With stirring, the mixture washeated to 70° C. on an oil bath, for 1 hour, with monitoring by TLC(eluent: 98:2 dichloromethane/methanol).

The yellow compound was drained, isolated by pouring the reactionmixture into water, on a frit and then washed with water several times.After drying under vacuum, in the presence of P₂O₅, 6.84 g of a yellowsolid corresponding to the expected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure.

Synthesis of 2-pyrrolidin-1-yl-pyrazolopyridine[1,5-a]pyridin-3-ylaminedihydrochloride

400 ml ethanol and 5 g of zinc powder were put in a 500-ml three-neckedflask equipped with a bulb condenser, a thermometer and a magneticstirrer, and brought to reflux.

Then 1 g of ammonium chloride dissolved in 0.5 ml of water was added,and 1 g of 3-nitro-2-pyrrolidin-1-yl-pyrazolo[1,5-a]pyridine was addedin portions in 15 minutes, and reflux was maintained for 4 hours.

At the end of reduction, the zinc was removed by filtration under argonon a bed of Celite and the filtrate was collected in a flask containing50 ml of previously cooled 6N hydrochloric isopropanol. The zinc waswashed with ethanol, the filtrates were combined and evaporated todryness.

After drying under vacuum, in the presence of P₂O₅ and soda tablets, 1.2g of a bluish powder corresponding to the expected compound wasobtained.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure.

¹H-NMR (DMSO-d₆): 1.91 (m, 4H), 3.46 (m, 1H), 6.70 (m, 1H), 7.21 (m,1H), 7.73 (m, 1H), 7.79 (se, 2H), 8.42 (m, 2H), 10.24 (se, 3H).

The quasi-molecular ions [M+H]⁺, [M+Na]⁺ of the expected moleculeC₁₁H₁₄N₄ were mainly detected.

Example 62-(3-Dimethylamino-pyrrolidin-1-yl)-pyrazolo[1,5-a]pyridin-3-ylaminedihydrochloride

Synthesis ofN,N-dimethyl-1-(3-nitropyrazolo[1,5-a]pyridin-2-yl)pyrrolidine-3-amine

5 ml of N-methypyrrolidinone, 3 g of2-(methylsulphonyl)-3-nitropyrazolo[1,5-a]pyridine and 3.77 ml of3-(dimethylamino)pyrrolidine were put in a 100-ml three-necked flaskequipped with a bulb condenser, a thermometer and a magnetic stirrer,and heated to 80° C. for one hour.

The reaction medium was poured onto a mixture of 200 g of ice and water.The yellow compound that crystallized was drained on a frit, washed with2×100 ml water and then with 3×100 ml isopropyl ether. After drying at35° C. under vacuum, in the presence of P₂O₅, for 12 hours, 3.26 g of ayellow solid corresponding to the expected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrophotometry were consistent with the expected structure.

Synthesis of2-(3-dimethylamino-pyrrolidin-1-yl)-pyrazolo[1,5-a]pyridin-3-ylaminedihydrochloride

400 ml ethanol and 5 g of zinc powder were put in a 500-ml three-neckedflask equipped with a bulb condenser, a thermometer and a magneticstirrer, and brought to reflux.

Then 1 g of ammonium chloride dissolved in 0.5 ml of water was added,and 1 g ofN,N-dimethyl-1-(3-nitropyrazolo[1,5-a]pyridin-2-yl)pyrrolidine-3-aminewas added in portions in 15 minutes, and reflux was maintained for 4hours.

At the end of reduction, the zinc was removed by filtration under argonon a bed of Celite and the filtrate was collected in a flask containing50 ml of previously cooled 6N hydrochloric isopropanol. The zinc waswashed with ethanol, the filtrates were combined and evaporated todryness.

After drying under vacuum, in the presence of P₂O₅ and soda tablets, 0.9g of a bluish powder corresponding to the expected compound wasobtained.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure. The quasi-molecular ions [M+H]⁺, [M+Na]⁺ ofthe expected molecule, C₁₃H₁₉N₅, were mainly detected.

Example 7 2-Imidazol-1-yl-pyrazolo[1,5-a]pyridin-3-ylaminedihydrochloride

Synthesis of 2-imidazol-1-yl-3-nitropyrazolo[1,5-a]pyridine

In a 100-ml three-necked flask equipped with a magnetic stirrer, athermometer and a condenser, 5 g of2-methanesulphanyl-3-nitropyrazolo[1,5-a]pyridine, ml ofN-methylpyrrolidinone and 7 g of imidazole were loaded successively.

This mixture was heated at 100° C. for 30 minutes then, after cooling,the 2-imidazol-1-yl-3-nitropyrazolo[1,5-a]pyridine was precipitated in 5volumes of water.

After draining and drying under vacuum in the presence of phosphoruspentoxide, 4.23 g of a yellow solid was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure. The mass of the expected compound,C₁₀H₇N₅O₂, was detected in mass spectrometry.

Synthesis of 2-imidazol-1-yl-pyrazolopyridine[1,5-a]pyridin-3-ylaminedihydrochloride

200 ml of ethanol and 6 g of zinc powder were put in a 500-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and brought to reflux.

Then 1 g of ammonium chloride dissolved in 0.5 ml of water was added,and 2 g of 2-imidazol-1-yl-3-nitropyrazolo[1,5-a]pyridine was added inportions in 15 minutes, and reflux was maintained for 4 h.

At the end of reduction, the zinc was removed by filtration under argonon a bed of Celite and the filtrate was collected in a flask containing50 ml of previously cooled 6N hydrochloric isopropanol. The zinc waswashed with ethanol, the combined liquors were concentrated to 1/3 andthe product formed was filtered on a frit.

After drying under vacuum, in the presence of P₂O₅ and soda tablets, 2.5g of a light pink powder corresponding to the expected compound wasobtained.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure.

¹H-NMR (DMSO-d₆): 7.07 (m, 1H), 7.37 (dd, 1H), 7.97 (m, 2H), 8.23 (dd,1H), 8.67 (d, 1H), 9.78 (se, 1H).

The quasi-molecular ions [M+H]⁺, [M+Na]⁺ of the expected molecule,C₁₀H₉N₅, were mainly detected.

Example 8N-2-(2-Pyrrolidin-1-ylethyl)pyrazolo[1,5-a]pyridine-2,3-diaminedihydrochloride

Synthesis of3-nitro-N-(2-pyrrolidin-1-ylethyl)pyrazolo[1,5-a]pyridin-2-amine

20 ml of N-methypyrrolidinone, 15 g (0.062 mol)2-methanesulphanyl-3-nitropyrazolo[1,5-a]pyridine and 16 ml of2,3-aminoethylpyrrolidine were put in a 100-ml three-necked flaskequipped with a bulb condenser, a thermometer and a magnetic stirrer.While being stirred, the mixture was heated to 80° C. on an oil bath for1 hour, monitoring by TLC (eluent: 90:5 ethyl acetate/methanol).

The reaction mixture was cooled to room temperature, then poured onto amixture of 400 g of ice and water. The yellowish-beige precipitate thatforms was drained on a frit and then washed several times with water.After drying at 35° C. under vacuum, in the presence of P₂O₅, 15.2 g ofa yellow solid corresponding to the expected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrometry were consistent with the expected structure.

Synthesis ofN-2-(2-pyrolidin-1-ylethyl)pyrazolo[1,5-a]pyridine-2,3-diaminedihydrochloride

200 ml of ethanol and 5 g of zinc powder were put in a 250-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and brought to reflux.

Then 2 ml of acetic acid were added dropwise, and then, in portions, 5 gof 3-nitro-N-(2-pyrrolidin-1-ylethyl)pyrazolo[1,5-a]pyridin-2-amine. Atthe end of discharge, 1 ml of acetic acid was added dropwise and refluxwas maintained for 2 hours.

At the end of reduction, the zinc was removed by filtration under argonon a bed of Celite and the filtrate was collected in a flask containing50 ml of previously cooled 6N hydrochloric isopropanol.

Precipitation of a greyish-blue solid was observed; this was drained ona No. 3 frit and then washed with 2×15 ml ethanol and 2×50 ml isopropylether. After drying under vacuum, in the presence of P₂O₅ and sodatablets, 5 g of a bluish powder corresponding to the expected compoundwas recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure.

¹H-NMR (DMSO d₆): 1.83 (m, 2H), 1.99 (m, 2H), 3.07 (m, 2), 3.38 (m, 2H),3.63 (m, 4H), 6.71 (m, 1H), 7.24 (m, 1H), 7.50 (d, 1H), 8.42 (d, 1H),10.13 (se, 1H), 10.25 (se, 3H).

The quasi-molecular ions [M+H]⁺, [M+Na]⁺, [M+Na+CH₃OH]⁺, [2M+H]⁺,[2M+Na]⁺ of the expected molecule, C₁₃H₁₉N₅, were mainly detected.

Example 9 2-(3-Amino-pyrazolo[1,5-a]pyridin-2-yloxy)-ethanoldihydrochloride

Synthesis of 2-[(3-nitropyrazolo[1,5-a]pyridin-2-yl)amino]ethanol

20 ml of ethylene glycol, 4.2 g of soda tablets dissolved in 10 ml waterand a solution of 2.5 g of2-methanesulphanyl-3-nitropyrazolo[1,5-a]pyridine and 20 ml ofN-methypyrrolidinone were put in a 100-ml three-necked flask equippedwith a bulb condenser, a thermometer and a magnetic stirrer. While beingstirred, the mixture was heated to 30° C. on an oil bath for 1 hour,with monitoring by TLC (eluent: 90:5 ethyl acetate/methanol).

The reaction mixture was cooled to room temperature and then poured intoa mixture of 450 g of ice and water. After being neutralized withhydrochloric acid, the yellowish-beige precipitate that formed wasdrained on a frit and then washed with water several times. After dryingat 35° C. under vacuum, in the presence of P₂O₅, 20.2 g of a yellowsolid corresponding to the expected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrometry were consistent with the expected structure.

Synthesis of 2-(3-amino-pyrazolo[1,5-a]pyridin-2-yloxy)-ethanoldihydrochloride

50 ml of ethanol and 5 ml of hydrochloric acid were put in a 100-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and then added in portions, under reflux, was amixture of 1.2 g of zinc and 500 mg ofmethanesulphanyl-3-nitropyrazolo[1,5-a]pyridine.

At the end of addition, reflux was maintained for 2 hours, then the zincwas removed by filtration under argon on a bed of Celite and thefiltrate was collected in a flask containing 50 ml of previously cooled6N hydrochloric isopropanol.

The filtrates were evaporated to dryness and taken up three times in asolution of hydrochloric ether followed by evaporation, to obtain athick blue liquid.

This liquid was poured progressively, with stirring and priming, onisopropyl ether. Precipitation of a blue solid was observed; this wasdrained on a No. 3 frit and washed with 2×50 ml of isopropyl ether.After drying under vacuum, in the presence of P₂O₅ and soda tablets, abluish powder corresponding to the expected compound was recovered.

Mass Analysis:

The quasi-molecular ions [M+H]⁺, [M+Na]⁺ and [M−H]⁻ of the expectedmolecule, C₉H₁₁N₃O₂, were mainly detected.

Example 10 2-Ethoxy-pyrazolo[1,5-a]pyridin-3-ylamine trihydrochloride

Synthesis of 2-ethoxy-3-nitropyrazolo[1,5-a]pyridine

50 ml of sodium ethylate and 4.9 g ofmethanesulphanyl-3-nitropyrazolo[1,5-a]pyridine were put in a 100-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and reflux for 0.5 h, with stirring.

The reaction mixture was stirred into 500 ml of water, the compound thatcrystallized was drained on a frit and washed with water then with 3×50ml of isopropyl ether. After drying at 35° C. under vacuum in thepresence of P₂O₅ for 12 hours, 4 g of a beige solid corresponding to theexpected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrometry were consistent with the expected structure.

Synthesis of 2-ethoxy-pyrazolo[1,5-a]pyridin-3-ylamine trihydrochloride

350 ml of ethanol and 12 g of zinc powder were put in a 500-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and brought to reflux.

Then 500 mg of ammonium chloride were added and then, in portions, 3.88g of 2-ethoxy-3-nitropyrazolo[1,5-a]pyridine.

At the end of addition, by maintaining reflux for 2 hours, reduction wascompleted. The zinc was removed by filtration under argon on a bed ofCelite and the filtrate was collected in a flask containing 50 ml ofpreviously cooled 6N hydrochloric isopropanol.

Precipitation of a solid was promoted by adding isopropyl ether to thefiltrate. The cream solid obtained was drained on a frit, and washedwith 2×15 ml of ethanol and 2×50 ml of isopropyl ether. After dryingunder vacuum, in the presence of P₂O₅ and soda tablets, a beige-creampowder corresponding to the expected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz D₂O) were consistent withthe expected structure.

¹H-NMR (D₂O): 1.45 (t, 3H), 4.43 (q, 2H), 6.91 (m, 1H), 7.41 (m, 1H),7.51 (m, 1H), 8.3 (m, 1H).

Mass Analysis:

The quasi-molecular ions [M+H]⁺, [M+Na]⁺ and [M−H]⁻ of the expectedmolecule, C₉H₁₁N₃O, were mainly detected.

Example 11N-2-(2-piperidin-1-ylethyl)pyrazolo[1,5-a]pyridine-2,3-diaminedihydrochloride

Synthesis of3-nitro-N-(2-piperidin-1-ylethyl)pyrazolo[1,5-a]pyridin-2-amine

100 ml of N-methypyrrolidinone, 20 g (0.0711 mol) of2-methanesulphanyl-3-nitropyrazolo[1,5-a]pyridine and 20.3 ml (0.142mol) of 2-piperidin-1-ylethane-amine were put in a 250-ml three-neckedflask equipped with a bulb condenser, a thermometer and a magneticstirrer. While being stirred, the mixture was heated to 70° C. on an oilbath for 4 hours, with monitoring by TLC (eluent: 95:5dichloromethane/methanol).

The reaction mixture was cooled to room temperature and poured onto amixture of 400 g of ice and water. The beige compound that crystallizedwas drained on a No. 4 frit and then washed with water several times.After drying at 35° C. under vacuum in the presence of P₂O₅, 20.43 g ofa yellow solid corresponding to the expected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure. The mass of the expected compound,C₁₄H₁₉N₅O₂, was detected in mass spectrometry.

The quasi-molecular ions [M+H]⁺, [M+Na]⁺, [M+Na+CH₃OH]⁺ of the expectedmolecule, C₁₄H₁₉N₅O₂, were mainly detected.

Synthesis ofN-2-(2-piperidin-1-ylethyl)pyrazolo[1,5-a]pyridine-2,3-diaminedihydrochloride

150 ml of ethanol and 2 g of zinc powder were put in a 250-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and brought to reflux.

Then 2 ml of acetic acid was added dropwise, and then in portions 2 g of3-nitro-N-(2-piperidin-1-ylethyl)pyrazolo[1,5-a]pyridin-2-amine was alsoadded dropwise. At the end of discharge, 1 ml of acetic acid was addeddropwise and reflux was maintained for 2 hours.

At the end of reduction, the zinc was removed by filtration under argonon a bed of Celite and the filtrate was collected in a flask containing50 ml of previously cooled 6N hydrochloric isopropanol.

Precipitation of a greyish-blue solid was observed. This was drained ona No. 3 frit and washed with 2×15 ml of ethanol and 2×50 ml of isopropylether. After drying under vacuum in the presence of P₂O₅ and sodatablets, 2 g of a greyish-blue powder corresponding to the expectedcompound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure.

Example 12N-2-[2-(diisopropylamino)ethyl]pyrazolo[1,5-a]pyridine-2,3-diaminedihydrochloride

Synthesis ofN,N-diisopropyl-N′-(3-nitropyrazolo[1,5-a]pyridin-2-yl)ethane-1,2-diamine

20 ml of N-methypyrrolidinone, 10 g (0.0414 mol) of2-methanesulphanyl-3-nitropyrazolo[1,5-a]pyridine and 14.4 ml (0.082mol) of N,N-diisopropylethane-1,2-diamine were put in a 100-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer. While being stirred, the mixture was heated to 70° C.on an oil bath for 1 hour, with monitoring by TLC (eluent: 95:5dichloromethane/methanol).

The reaction mixture was cooled to room temperature, and poured onto amixture of 100 g of ice and water. The yellow precipitate that forms wasdrained on a No. 3 frit, then washed with water and then with 3×100 mlof petroleum ether. After drying at 35° C. under vacuum in the presenceof P₂O₅, 11.88 g of a yellow solid corresponding to the expectedcompound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure. The quasi-molecular ions [M+H]⁺, [M+Na]⁺,[M+Na+CH₃OH]⁺ of the expected molecule, C₁₅H₂₃N₅O₂ were mainly detected.

Synthesis ofN-2-[2-(diisopropylamino)ethyl]pyrazolo[1,5-a]pyridine-2,3-diaminedihydrochloride

150 ml of ethanol and 2 g of zinc powder were put in a 250-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and brought to reflux.

Then 1.75 ml of acetic acid were added dropwise and then, in portions,1.75 g ofN,N-diisopropyl-N′-(3-nitropyrazolo[1,5-a]pyridin-2-yl)ethane-1,2-diaminewas also added dropwise. At the end of discharge, 1 ml of acetic acidwere added dropwise, and reflux was maintained for 2 hours.

At the end of reduction, the zinc was removed by filtration under argonon a bed of Celite and the filtrate was collected in a flask containing50 ml of previously cooled 6N hydrochloric isopropanol.

Precipitation of a greyish-blue solid was then observed. This wasdrained on a No. 3 frit, and washed with 2×15 ml of ethanol and 2×50 mlof isopropyl ether. After drying under vacuum in the presence of P₂O₅and soda tablets, a greyish-blue powder corresponding to the expectedcompound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure.

The mass of the expected compound C₁₅H₂₅N₅ was detected in massspectrometry.

The quasi-molecular ions [M+H]⁺, [M+Na]⁺, [M+Na+CH₃OH]⁺ of the expectedmolecule, C₁₅H₂₅N₅, were mainly detected.

Example 13N-2-[2-(diethylamino)ethyl]pyrazolo[1,5-a]pyridine-2,3-diaminedihydrochloride

Synthesis ofN,N-diethyl-N′-(3-nitropyrazolo[1,5-a]pyridin-2-yl)ethane-1,2-diamine

100 ml of N-methypyrrolidinone, 10 g (0.0414 mol)2-methanesulphanyl-3-nitropyrazolo[1,5-a]pyridine and 11.65 ml (0.0829mol) of N,N-diethylenediamine were put in a 100-ml three-necked flaskequipped with a bulb condenser, a thermometer and a magnetic stirrer.While being stirred, the mixture was heated to 70° C. on an oil bath for4 hours.

The reaction mixture was cooled to room temperature and poured onto amixture of 100 g of ice and water. The yellow compound that crystallizedwas drained on a No. 3 frit and then washed with 3×100 ml of petroleumether. After drying at 35° C. under vacuum in the presence of P₂O₅, 9.80g of a yellow solid corresponding to the expected compound wasrecovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure. The quasi-molecular ions [M+H]⁺, [M+Na]⁺,[M+Na+CH₃OH]⁺ of the expected molecule, C₁₃H₁₉N₅O₂ were mainly detected.

Synthesis ofN-2-[2-(diethylamino)ethyl]pyrazolo[1,5-a]pyridine-2,3-diaminedihydrochloride

150 ml of ethanol and 2 g of zinc powder were put in a 250-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and brought to reflux.

Then added dropwise were 2 ml of acetic acid and then, in portions, 2 gofN,N-diisopropyl-N′-(3-nitropyrazolo[1,5-a]pyridin-2-yl)ethane-1,2-diamine.At the end of discharge, 1 ml of acetic acid was added dropwise, andreflux was maintained for 2 hours.

At the end of reduction, the zinc was removed by filtration under argonon a bed of Celite and the filtrate was collected in a flask containing50 ml of previously cooled 6N hydrochloric isopropanol.

Precipitation of a greyish-blue solid was then observed. This wasdrained on a frit, and washed with 2×15 ml of ethanol and 2×50 ml ofisopropyl ether. After drying under vacuum in the presence of P₂O₅ andsoda tablets, 2 g of a greyish-green powder corresponding to theexpected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure.

The mass of the expected compound C₁₃H₂₁N₅ was detected in massspectrometry.

The quasi-molecular ions [M+H]⁺, [M+Na]⁺, [M+Na+CH₃OH]⁺ of the expectedmolecule, C₁₃H₂₁N₅, were mainly detected.

Example 14 N-2-(2-pyridin-3-ylethyl)pyrazolo[1,5-a]pyridine-2,3-diaminedihydrochloride

Synthesis of3-nitro-N-(2-pyridin-3-ylethyl)pyrazolo[1,5-a]pyridin-2-amine

10 ml of N-methypyrrolidinone, 4.93 g (0.02046 mol)2-methanesulphanyl-3-nitropyrazolo[1,5-a]pyridine and 5 g ml (0.04092mol) of 3-(2-aminoethyl)-pyridine were put in a 100-ml three-neckedflask equipped with a bulb condenser, a thermometer and a magneticstirrer. While being stirred, the mixture was heated to 70° C. on an oilbath for 1 hour.

The reaction mixture was cooled to room temperature and then poured ontoa mixture of 100 g of ice and water. The yellow compound thatcrystallized was drained on a frit, washed with water and then with3×100 ml of petroleum ether. After drying at 350° C. under vacuum in thepresence of P₂O₅, 5.61 g of a yellow solid corresponding to the expectedcompound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure.

The quasi-molecular ions [M+H]⁺, [M+Na]⁺, [M+Na+CH₃OH]⁺, [2M+H]⁺,[2M+Na]⁺ of the expected molecule C₁₄H₁₃N₅O₂ were mainly detected.

Synthesis ofN-2-(2-pyridin-3-ylethyl)pyrazolo[1,5-a]pyridine-2,3-diaminedihydrochloride

150 ml of ethanol and 2 g of zinc powder were put in a 250-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and brought to reflux.

Then added dropwise were 2 ml of acetic acid and then, in portions, 1.6g of 3-nitro-N-(2-pyridin-3-ylethyl)pyrazolo[1,5-a]pyridin-2-amine. Atthe end of discharge, 1 ml of acetic acid was added dropwise, and refluxwas maintained for 2 hours.

At the end of reduction, the zinc was removed by filtration under argonon a bed of Celite and the filtrate was collected in a flask containing50 ml of previously cooled 6N hydrochloric isopropanol.

Precipitation of a greyish-blue solid was then observed. This wasdrained on a No. 3 frit and washed with 2×15 ml of ethanol and 2×50 mlof isopropyl ether. After drying under vacuum in the presence of P₂O₅and soda tablets, 1.46 g of a greyish-green powder corresponding to theexpected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure.

The quasi-molecular ions [M+H]⁺, [M+Na]⁺, [M+Na+CH₃OH]⁺, [2M+H]⁺,[2M+Na]⁺ of the expected molecule, C₁₄H₁₅N₅, were mainly detected.

Example 15 N-2-(2-pyridin-4-ylethyl)pyrazolo[1,5-a]pyridine-2,3-diaminedihydrochloride

Synthesis of3-nitro-N-(2-pyridin-4-ylethyl)pyrazolo[1,5-a]pyridin-2-amine

50 ml of N-methypyrrolidinone, 10 g (0.03555 mol)2-methanesulphanyl-3-nitro-pyrazolo[1,5-a]pyridine and 8.68 g (0.07110mol) of 4-(2-aminoethyl) were put in a 100-ml three-necked flaskequipped with a bulb condenser, a thermometer and a magnetic stirrer.While being stirred, the mixture was heated to 70° C. on an oil bath for4 hours, with monitoring by TLC (eluent: 95:5 dichloromethane/methanol).

The reaction mixture was cooled to room temperature and poured onto amixture of 200 g of ice and water. The yellow compound that crystallizedwas drained on a No. 3 frit, and washed with water and then with 3×100ml of petroleum ether. After drying at 35° C. under vacuum in thepresence of P₂O₅ for 12 hours, 10.81 g (product not totally dry) of ayellow solid corresponding to the expected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure.

Synthesis ofN-2-(2-pyridin-4-ylethyl)pyrazolo[1,5-a]pyridine-2,3-diaminedihydrochloride

150 ml of ethanol and 2 g of zinc powder were put in a 250-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and brought to reflux.

Then added dropwise were 2 ml of acetic acid and then, in portions, 2 gof 3-nitro-N-(2-pyridin-4-ylethyl)pyrazolo[1,5-a]pyridin-2-amine. At theend of discharge, 1 ml of acetic acid was added dropwise, and reflux wasmaintained for 2 hours.

At the end of reduction, the zinc was removed by filtration under argonon a bed of Celite and the filtrate was collected in a flask containing50 ml of previously cooled 6N hydrochloric isopropanol.

Precipitation of a greyish-blue solid was then observed. This wasdrained on a frit and washed with 2×15 ml of ethanol and 2×50 ml ofisopropyl ether. After drying under vacuum in the presence of P₂O₅ andsoda tablets, 1.8 g of a greyish-green powder corresponding to theexpected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure.

¹H-NMR (DMSO-d₆): 3.21 (t, 2H), 3.64 (t, 2H), 6.66 (m, 1), 7.19 (m, 1H),7.50 (m, 1H), 8.04 (d, 2H), 8.39 (m, 1H), 8.82 (d, 2H).

The quasi-molecular ions [M+H]⁺, [M+Na]⁺, [M+Na+CH₃OH]⁺, [2M+H]⁺,[2M+Na]⁺ of the expected molecule, C₁₄H₁₅N₅, were mainly detected.

Example 16N-2-[2-(4-methylpiperazin-1-yl)ethyl]pyrazolo[1,5-a]pyridine-2,3-diaminedihydrochloride

Synthesis ofN-[2-(4-methylpiperazin-1-yl)ethyl]-3-nitropyrazolo[1,5-a]pyridin-2-amine

10 ml of N-methypyrrolidinone, 7.23 g (0.03 mol)2-methanesulphanyl-3-nitro-pyrazolo[1,5-a]pyridine and 10 ml (0.1 mol)of N-methylpiperidine were put in a 50-ml three-necked flask equippedwith a bulb condenser, a thermometer and a magnetic stirrer. While beingstirred, the mixture was heated to 70° C. on an oil bath for 4 hours.

The reaction mixture was cooled to room temperature and poured onto amixture of 400 g of ice and water. The beige compound that crystallizedwas drained on a frit and then washed with water several times. Afterdrying at 35° C. under vacuum in the presence of P₂O₅, 7.99 g of ayellow solid corresponding to the expected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure.

The mass of the expected compound C₁₂H₁₅N₅O₂ was detected in massspectrometry.

The quasi-molecular ions [M+H]⁺, [M+Na]⁺, [M+Na+CH₃OH]⁺ of the expectedmolecule C₁₂H₁₅N₅O₂ were mainly detected.

Synthesis ofN-2-[2-(4-methylpiperazin-1-yl)ethyl]pyrazolo[1,5-a]pyridine-2,3-diaminedihydrochloride

200 ml ethanol and 6 g of zinc powder were put in a 500-ml three-neckedflask equipped with a bulb condenser, a thermometer and a magneticstirrer, and brought to reflux.

Then 1 g of ammonium chloride dissolved in 0.5 ml of water was added,and then 2 g ofN-[2-(4-methylpiperazin-1-yl)ethyl]-3-nitropyrazolo[1,5-a]pyridin-2-aminewas added in portions in 15 minutes, and reflux was maintained for 2hours.

At the end of reduction, the zinc was removed by filtration under argonon a bed of Celite and the filtrate was collected in a flask containing50 ml of previously cooled 6N hydrochloric isopropanol, washed withethanol and the combined filtrates were diluted with isopropyl ether.The solid that formed was drained on a frit.

After drying under vacuum in the presence of P₂O₅ and soda tablets, 0.3g of a light bluish-green powder corresponding to the expected compoundwas obtained.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure.

Example 17 2-methoxy-7-methyl-pyrazolopyridine[1,5-a]pyridin-3-ylaminehydrochloride

Synthesis of 1-amino-2-methylpyridinium iodide

400 ml of water and 100 g of picoline were put in a 2-liter three-neckedflask equipped with a bulb condenser, a thermometer, a magnetic stirrerand a dropping funnel and, at 30° C., then quickly the solution of 40.1g of hydroxylaminosulphonic acid in 600 ml of water was added, and themixture was heated at 85° C. for 6 hours, and then stirring wasmaintained at room temperature overnight.

After the addition of 69.3 g of potassium carbonate, 4×500 ml of ethylacetate were extracted and the aqueous phase was evaporated. The solidthat formed was taken up in 1.5 liter of ethanol.

After removal of the salts, the liquor was acidified at −60° C. with47.3 ml of hydriodic acid.

Stirring was continued for 1 hour, and the solid was precipitated with400 ml of isopropyl ether. The solid that formed was taken up inpetroleum ether, drained on a frit and then washed with petroleum ether.

After drying under vacuum in the presence of P₂O₅, 37.6 g of achestnut-brown solid corresponding to the expected compound wasrecovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrophotometry were consistent with the expected structure.

Synthesis of 7-methyl-2-(methylsulphanyl)-3-nitropyrazolo[1,5-a]pyridine

200 ml of DMF, 400 ml of ethanol, 34 g of 1,1-amino-2-methylpyridiniumiodide, and 32 ml of triethylamine were put in a 500-ml three-neckedflask equipped with a bulb condenser, a thermometer, a magnetic stirrer,and a dropping funnel, and stirred for 30 minutes.

The solution of 25.9 g of 1,1-bis(methylthio)-2-nitroethylene in 200 mlof DMF was added, and the reaction mixture was refluxed for 24 hours.

After cooling to room temperature, the reaction mixture was poured onto4 liters of ice-water mixture.

The chestnut-brown insoluble product that formed was drained on a frit,washed with water and acetone, and after drying under vacuum in thepresence of P₂O₅, 15.9 g of an ochre-brown solid corresponding to theexpected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrometry were consistent with the expected structure.

Synthesis of 7-methyl-2-(methylsulphonyl)-3-nitropyrazolo[1,5-a]pyridine

400 ml of dichloromethane and 3.2 g of7-methyl-2-(methylsulphanyl)-3-nitropyrazolo[1,5-a]pyridine were put ina 1 L three-necked flask equipped with a bulb condenser, a thermometerand a magnetic stirrer and a dropping funnel, then, at 10° C., addeddropwise was a solution of 13.2 g of meta-chloroperbenzoic acid in 250ml of dichloromethane over 2 hours.

Stirring was maintained for several hours and the reaction mixturerecovered was washed with 2×500 ml of saturated solution of sodiumhydrogencarbonate and then 500 ml water.

The organic phase was washed several times with water and after dryingover sodium sulphate the organic phase was evaporated to dryness, thenafter drying at 35° C. under vacuum in the presence of P₂O₅ for 12hours, 2.33 g of a dull yellow solid corresponding to the expectedcompound was obtained.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrometry were consistent with the expected structure.

Synthesis of 2-methoxy-7-methyl-3-nitropyrazolo[1,5-a]pyridine

15 ml of 30% sodium methylate and 2 g of7-methyl-2-(methylsulphonyl)-3-nitropyrazolo[1,5-a]pyridine were put ina 100-ml three-necked flask equipped with a bulb condenser, athermometer and a magnetic stirrer.

Stirring was continued for 2 hours and the reaction mixture was pouredinto 500 ml of water. The pH was adjusted to 7 by adding hydrochloricacid, the compound that crystallized was drained on a frit and washedwith water and then with 3×50 ml of isopropyl ether. After drying at 35°C. under vacuum in the presence of P₂O₅ for 12 hours, 1.62 g of a beigesolid corresponding to the expected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrometry were consistent with the expected structure.

Synthesis of 2-methoxy-7-methyl-pyrazolo[1,5-a]pyridin-3-ylaminehydrochloride

40 ml of ethanol and 4 g of zinc powder were put in a 100-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and brought to reflux.

Added dropwise were 10 ml of 35% hydrochloric acid and then, inportions, 1.8 g of 2-methoxy-7-methyl-3-nitropyrazolo[1,5-a]pyridine.

At the end of addition, a few drops of hydrochloric ethanol were addedand reflux was maintained for 1 hour.

At the end of reduction, the zinc was removed by filtration under argonon a bed of Celite and the filtrate was collected in a flask containing20 ml of previously cooled 6N hydrochloric ethanol and afterconcentrating to 1/3, ethyl acetate was added to the residue, thenevaporated to the maximum.

The residue was taken up in hydrochloric ethanol and the solid thatformed was drained on a frit, then washed with 2×50 ml of isopropylether. After drying under vacuum in the presence of P₂O₅ and sodatablets, 1.2 g of a powder corresponding to the expected compound wasrecovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz D₂O) were consistent withthe expected structure.

Mass Analysis:

The quasi-molecular ions [M+H]⁺, [M+Na]⁺ and [M−H]⁻ of the expectedmolecule, C₉H₁₁N₃O, were mainly detected.

Example 18 4-Ethyl-2-methoxy-7-methyl-pyrazolo[1,5-a]pyridin-3-ylaminedihydrochloride

Synthesis of 1-amino-5-ethyl-2-methylpyridinium iodide

100 ml of water and 50 ml of 5-ethyl-2-methylpyridine were put in a500-ml three-necked flask equipped with a bulb condenser, a thermometer,a magnetic stirrer and a dropping funnel and, at 30° C., a solution of20 g of hydroxylaminosulphonic acid in 250 ml of water was quickly addedand the reaction mixture was heated at 85° C. for 6 hours, then stirringwas continued at room temperature overnight.

Extraction was carried out with 5×500 ml of ethyl acetate and theaqueous phase was evaporated to dryness, and the solid obtained waswashed with 500 ml of ethanol.

The ethanolic liquor was put in a 1-liter three-necked flask, cooled to−40° C. and 29 ml of hydriodic acid was quickly added dropwise whilestirring well.

Stirring was continues for one hour and the solid obtained wasprecipitated with 3 liters of isopropyl ether. The salmon-pink solidthat formed was drained on a frit and then washed with isopropyl ether.

After drying under vacuum in the presence of P₂O₅, 15.2 g of anochre-brown solid corresponding to the expected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrophotometry were consistent with the expected structure.

Synthesis of4-ethyl-7-methyl-2-(methylsulphanyl)-3-nitropyrazolo[1,5-a]pyridine

160 ml of DMF, 24.8 g of 1-amino-5-ethyl-2-methylpyridinium iodide, 39 gof potassium carbonate and 15.5 g of 1,1-bis(methylthio)-2-nitroethylenewere put in a 500-ml three-necked flask equipped with a bulb condenser,a thermometer, a magnetic stirrer and a dropping funnel.

Stirring was continued for 96 hours at room temperature and the reactionmixture was then poured onto 2.5 liters of ice-water mixture.

The ochre-brown insoluble matter that formed was drained on a No. 3frit, washed with plenty of water, with 3×50 ml of isopropanol and thenwith 3×500 ml of isopropyl ether.

After drying under vacuum in the presence of P₂O₅, 10.59 g of anochre-brown solid corresponding to the expected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrophotometry were consistent with the expected structure.

The quasi-molecular ions [M+H]⁺, [M+Na]⁺, [M+Na+CH₃OH]⁺, [2M+Na]⁺ weremainly detected.

Synthesis of4-ethyl-7-methyl-2-(methylsulphonyl)-3-nitropyrazolo[1,5-a]pyridine

100 ml of dichloromethane and 10 g of4-ethyl-7-methyl-2-(methylsulphanyl)-3-nitropyrazolo[1,5-a]pyridine wereput in a 1 L three-necked flask equipped with a bulb condenser, athermometer, a magnetic stirrer and a dropping funnel then, at 10° C., asolution of 39.2 g of meta-chloroperbenzoic acid in 600 ml ofdichloromethane was added dropwise in 2 hours.

Stirring was continued for one more hour and the reaction mixture waswashed with 4×500 ml of saturated solution of sodium hydrogencarbonateand then 500 ml of water.

After drying, the organic phase was evaporated to dryness, and theyellow compound that formed was taken up in isopropyl ether.

The solid was drained on a frit, washed with water and then with 3×50 mlof isopropyl ether. After drying at 35° C. under vacuum in the presenceof P₂O₅ for 12 hours, a yellow solid corresponding to the expectedcompound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrophotometry were consistent with the expected structure.

The quasi-molecular ions [M+H]⁺, [M+Na]⁺, [M+Na+CH₃OH]⁺, [2M+Na]⁺ weremainly detected.

Synthesis of 4-ethyl-2-methoxy-7-methyl-3-nitropyrazolo[1,5-a]pyridine

30 ml of 30% sodium methylate and 4 g of4-ethyl-7-methyl-2-(methylsulphonyl)-3-nitropyrazolo[1,5-a]pyridine in30 ml of methanol were put in a 100-ml three-necked flask equipped witha bulb condenser, a thermometer and a magnetic stirrer, and stirred for2 hours.

The reaction mixture was poured onto 500 ml of water, the compound thatcrystallized was drained on a frit, and washed with water and then with3×50 ml of isopropyl ether. After drying at 35° C. under vacuum in thepresence of P₂O₅ for 12 hours, 1.2 g of a beige solid corresponding tothe expected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrophotometry were consistent with the expected structure.

The quasi-molecular ions [M+H]⁺, [M+Na]⁺, [M+Na+CH₃OH]⁺, [2M+Na]⁺ weremainly detected.

Synthesis of 4-ethyl-2-methoxy-7-methyl-pyrazolo[1,5-a]pyridin-3-ylaminedihydrochloride

50 ml of ethanol and 4.5 g of zinc powder were put in a 100-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and brought to reflux.

Next, 175 mg of ammonium chloride were added and then, in portions, 620mg of 4-ethyl-2-methoxy-7-methyl-3-nitropyrazolo[1,5-a]pyridine. At theend of addition, ml of hydrochloric ethanol were added dropwise andreflux was maintained for 1 hour.

At the end of reduction, the zinc was removed by filtration under argonon a bed of Celite and the filtrate was collected in a flask containing20 ml of previously cooled 6N hydrochloric ethanol and afterconcentrating to 1/3, the liquor was diluted with 400 ml of isopropylether.

Precipitation of a sticky solid was observed; this was taken up inisopropyl ether. Once it crystallized, the solid was drained on a fritand then washed with 2×50 ml of isopropyl ether. After drying undervacuum in the presence of P₂O₅ and soda tablets, 1.5 g of a powdercorresponding to the expected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure.

The quasi-molecular ions [M+H]⁺, [M+Na]⁺ and [M−H]⁻ of the expectedmolecule, C₁₁H₁₅N₃O, were mainly detected.

Example 194-ethyl-7-methyl-2-pyrrolidin-1-yl-pyrazolo[1,5-a]pyridin-3-ylaminedihydrochloride

Synthesis of4-ethyl-7-methyl-3-nitro-2-pyrrolidin-1-ylpyrazolo[1,5-a]pyridine

25 ml of pyrrolidine and 1.5 g of4-ethyl-7-methyl-2-(methylsulphanyl)-3-nitropyrazolo[1,5-a]pyridine wereput in a 50-ml three-necked flask equipped with a bulb condenser, athermometer and a magnetic stirrer; this mixture was stirred for 1 hour.

The yellow compound was drained, isolated by pouring the reactionmixture into ice water, on a frit and then washed with water severaltimes and with petroleum ether. After drying under vacuum in thepresence of P₂O₅, 0.651 g of a yellow solid corresponding to theexpected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure.

Synthesis of4-ethyl-7-methyl-2-pyrrolidin-1-yl-pyrazolo[1,5-a]pyridin-3-ylaminedihydrochloride

30 ml of ethanol and 1.6 g of zinc powder were put in a 50-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and brought to reflux.

Then 60 mg of ammonium chloride were added, then, in portions, 620 mg of4-ethyl-7-methyl-3-nitro-2-pyrrolidin-1-ylpyrazolo[1,5-a]pyridine.

At the end of addition, 5 ml of hydrochloric ethanol were added dropwiseand reflux was maintained for 2 hours.

At the end of reduction, the zinc was removed by filtration under argonon a bed of Celite and the filtrate was collected in a flask containing20 ml of previously cooled 6N hydrochloric ethanol, and isopropyl etherwas added to this filtrate.

Precipitation of a yellowish solid was then observed. This was drainedon a frit and washed with 2×50 ml of isopropyl ether. After drying undervacuum in the presence of P₂O₅ and soda tablets, 623 mg of agreyish-beige powder corresponding to the expected compound wasrecovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz D₂O) were consistent withthe expected structure.

The quasi-molecular ions [M+H]⁺, [M+Na]⁺ and [M−H] of the expectedmolecule, C₁₄H₂₀N₄, were mainly detected.

Example 20 2-Methylsulphanyl-pyrazolo[1,5-a]pyridin-3-ylaminehydrochloride

Synthesis of 2-methylsulphanyl-pyrazolo[1,5-a]pyridin-3-ylaminehydrochloride

200 ml of ethanol and 15 g of zinc powder were put in a 500-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and brought to reflux.

Then added dropwise were 5 ml of hydrochloric acid, then, in portions, 5g of 2-(methylsulphanyl)-3-nitropyrazolo[1,5-a]pyridine in 45 minutes.At the end of addition, ml of hydrochloric acid was added dropwise andreflux was maintained for 2 hours.

At the end of reduction, the zinc was removed by filtration under argonon a bed of Celite and the filtrate was collected in a flask containing50 ml of previously cooled 6N hydrochloric isopropanol.

Precipitation of a beige solid was observed. This was drained on a fritand was then washed with 2×50 ml of isopropyl ether. After drying undervacuum in the presence of P₂O₅ and soda tablets, 4.9 g of agreyish-beige powder corresponding to the expected compound wasrecovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure.

The quasi-molecular ions [M+H]⁺, [M+Na]⁺ and [M−H]⁻ of the expectedmolecule, C₈H₉N₃S, were mainly detected.

Example 216,7-Dimethyl-2-methylsulphanyl-pyrazolo[1,5-a]pyridin-3-ylaminedihydrochloride

Synthesis of 1-amino-2,3-dimethylpyridinium iodide

400 ml of water and 64.2 g of 2,3-dimethylpyridine were put in a 1-literthree-necked flask, heated to 30° C. then 122.6 g ofhydroxylamine-o-sulphonic acid were added.

At the end of addition, the reaction mixture was heated at 90° C. for 7hours. After cooling to room temperature, 28 g of potassium carbonatewere added in portions in an hour, with stirring.

Then the aqueous solution was washed with 5×300 ml of ethyl acetate andthe residue was taken up in 200 ml of ethanol, the solid obtained wasfiltered and 56.9 g of 45% hydriodic acid was added dropwise to thefiltrate cooled to −60° C.

Stirring was continued for two hours and the solid that formed wasdrained on a No. 3 frit. After drying under vacuum in the presence ofP₂O₅, 31.5 g of 1-amino-2,3-dimethylpyridinium iodide corresponding tothe expected compound was recovered.

¹H-NMR (200 MHz, CDCl₃), □ 8.06 (d, 1H), 7.46 (d, 1H), 2.76 (s, 3H),2.67 (s, 3H), 2.43 (s, 3H)

Synthesis of6,7-dimethyl-2-(methylsulphanyl)-3-nitropyrazolo[1,5-a]pyridine

19.1 g of triethylamine was added dropwise to a 1-liter round-bottomedflask containing 800 ml of anhydrous ethanol, 31.5 g of1-amino-2,3-dimethylpyridinium iodide and 20.8 g of1,1-bis(methylthio)-2-nitroethylene.

The reaction mixture was refluxed for 3 hours and then cooled to atemperature below 10° C. The solid that formed was drained whilestirring, washed with ethanol, and after drying under vacuum in thepresence of P₂O₅, 8.32 g of6,7-dimethyl-2-(methylsulphanyl)-3-nitropyrazolo[1,5-a]pyridinecorresponding to the expected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrometry were consistent with the expected structure.

Synthesis of6,7-dimethyl-2-methylsulphanyl-pyrazolo[1,5-a]pyridin-3-ylaminedihydrochloride

100 ml of ethanol and 10 g of zinc powder were put in a 250-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and brought to reflux.

Then added dropwise was 1 ml of 35% hydrochloric acid and then, inportions, 4 g of6,7-dimethyl-2-(methylsulphanyl)-3-nitropyrazolo[1,5-a]pyridine.

At the end of addition, reflux was maintained for 2 hours. At the end ofreduction, the zinc was removed by filtration under argon on a bed ofCelite and the filtrate was collected in a flask containing 50 ml ofpreviously cooled 6N hydrochloric isopropanol.

The filtrate was concentrated to 1/3 of volume; and crystallization of agrey solid was observed. This was drained on a frit and then washed with2×100 ml of isopropyl ether. After drying under vacuum in the presenceof P₂O₅ and soda tablets, 3.6 g of a grey powder corresponding to theexpected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) were consistentwith the expected structure.

The quasi-molecular ions [M+H]⁺, [M+Na]⁺ and [M−H]⁻ of the expectedmolecule, C₁₀H₁₃N₃S, were mainly detected.

Example 22N-2-[2-(dimethylamino)ethyl]-6,7-dimethylpyrazolo[1,5-a]pyridine-2,3-diaminedihydrochloride

Synthesis ofN-2-[2-(dimethylamino)ethyl]-6,7-dimethylpyrazolo[1,5-a]pyridine-2,3-diaminedihydrochloride

200 ml of ethanol and 5 g of zinc powder were put in a 500-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and brought to reflux.

Then added dropwise was 1 ml of acid acetic and then, in portions, 4 gofN′-(6,7-dimethyl-3-nitropyrazolo[1,5-a]pyridin-2-yl)-N,N-dimethylethane-1,2-diamine,while regularly adding acetic acid (to a total of 1.5 ml).

At the end of addition, reflux was maintained for 2 hours. At the end ofreduction, the zinc was removed by filtration under argon on a bed ofCelite and the filtrate was collected in a flask containing 100 ml ofpreviously cooled 6N hydrochloric isopropanol.

A white solid crystallized; it was drained on a frit and then washedwith 2×100 ml of isopropyl ether. After drying under vacuum in thepresence of P₂O₅ and soda tablets, 4.5 g of a white powder correspondingto the expected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrometry were consistent with the expected structure.

Example 22 2-methoxy-6,7-dimethylpyrazolo[1,5-a]pyridin-3-aminehydrochloride

Synthesis of 2-methoxy-6,7-dimethylpyrazolo[1,5-a]pyridin-3-aminehydrochloride

100 ml of ethanol and 1.5 g of zinc powder were put in a 250-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and brought to reflux.

Then 3 drops of acetic acid were added and then, in portions, 1.5 g of2-methoxy-6,7-dimethyl-3-nitropyrazolo[1,5-a]pyridine while regularlyadding a few drops of acetic acid.

At the end of addition, reflux was maintained for 20 minutes. At the endof reduction, the zinc was removed by filtration under argon on a bed ofCelite and the filtrate was collected in a flask containing 20 ml ofpreviously cooled 6N hydrochloric isopropanol.

After evaporating the solution to 1/10, crystallization was started andabundant beige solid crystallized on adding 50 ml of a mixture ofisopropanol and ether.

The solid was drained on a frit and then washed with 2×30 ml of ether.After drying under vacuum in the presence of P₂O₅ and soda tablets, 700mg of a white powder corresponding to the expected compound wasrecovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrometry were consistent with the expected structure.

Example 23 2-isopropoxy-6,7-dimethylpyrazolo[1,5-a]pyridin-3-aminehydrochloride

Synthesis of 2-isopropoxy-6,7-dimethylpyrazolo[1,5-a]pyridin-3-aminehydrochloride

100 ml of ethanol and 1.5 g of zinc powder were put in a 250-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and brought to reflux.

Then 0.25 ml of acetic acid were added and then, in portions, 1.5 g of2-isopropoxy-6,7-dimethyl-3-nitropyrazolo[1,5-a]pyridine while regularlyadding a few drops of acetic acid.

At the end of addition, reflux was maintained for 1 hour. At the end ofreduction, the zinc was removed by filtration under argon on a bed ofCelite and the filtrate was collected in a flask containing 20 ml ofpreviously cooled 6N hydrochloric isopropanol.

After evaporating the solution to 1/10, 50 ml of heptane was added andthe solution was concentrated again to 1/10 of volume; then taken up in50 ml of ether to start crystallization. The solid that formed wasdrained on a frit. After drying under vacuum in the presence of P₂O₅ andsoda tablets, 560 mg of a slightly pink beige powder corresponding tothe expected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrometry were consistent with the expected structure.

Example 24N-5,N-5-dimethyl-2-methylsulphanyl-pyrazolo[1,5-a]pyridine-3,4-diaminedihydrochloride

Synthesis ofN-5,N-5-dimethyl-2-methylsulphanyl-pyrazolo[1,5-a]pyridine-3,4-diaminedihydrochloride

100 ml of ethanol and 6 g of zinc powder were put in a 250-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and brought to reflux.

Then added dropwise was 1 ml of hydrochloric acid and then, in portions,2.36 g ofN,N-dimethyl-2-(methylsulphanyl)-3-nitropyrazolo[1,5-a]pyridin-5-amine.

At the end of addition, reflux was maintained for 2 hours. At the end ofreduction, the zinc was removed by filtration under argon on a bed ofCelite and the filtrate was collected in a flask containing 50 ml ofpreviously cooled 6N hydrochloric isopropanol.

The liquor was concentrated to 1/8 of volume; and crystallization of abeige solid was observed. This was taken up in hydrochloric isopropanol.The solid that formed was drained on a frit and then wash with 2×100 mlof isopropyl ether. After drying under vacuum in the presence of P₂O₅and soda tablets, 2.4 g of a grey powder corresponding to the expectedcompound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrometry were consistent with the expected structure.

Example 25N-2-[2-(dimethylamino)ethyl]-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridine-2,3-diamine

Synthesis of 1-amino-6,7-dihydro-5H-cyclopenta[b]pyridinium iodide

400 ml of water and 123 g (1.032 mol) of 2,3-cyclopentenopyridine wereput in a 1000-ml three-necked flask equipped with a bulb condenser, athermometer and a mechanical stirrer, then 46.6 g (0.413 mol) ofhydroxylamine-o-sulphonic acid was added in small portions and refluxwas carried out for 18 hours.

The reaction mixture was cooled to room temperature and 74.2 g (0.537mol) of potassium carbonate was gently added, then stirred for 30minutes.

The aqueous phase was washed with 4×200 ml of ethyl acetate, thenco-evaporated with 2-propanol to obtain a chestnut-brown solid; this wastaken up in 400 ml of ethanol to remove the salts.

The brown ethanol solution was put in a 2-liter three-necked flaskequipped with an isobaric funnel and cooled to −50° C. with stirring.Then added, dropwise, were 67.5 ml (0.516 mol) of hydriodic acid.

At the end of addition, the temperature was returned to zero degrees andthe beige insoluble matter was drained on a frit. This solid was washedwith 3×150 ml of isopropyl ether. After drying under vacuum in thepresence of P₂O₅ for 12 hours, 27.7 g of a beige solid corresponding tothe expected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrometry were consistent with the expected structure.

The expected cation [C₈H₁₁N₂]⁺ was mainly detected at m/z, ESP+=135.Detection of I⁻ ions in electrospray was negative.

Synthesis of2-(methylsulphanyl)-3-nitro-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridine

500 ml of N-methylpyrrolidinone and 65.56 g (0.025 mol) of1-amino-6,7-dihydro-5H-cyclopenta[b]pyridinium iodide were put in a2-liter three-necked flask equipped with a bubbler, a condenser and amechanical stirrer. Gently added, while stirring, were 103.65 g ofpotassium carbonate in 15 minutes and then, in one go, 41.33 g (0.25mol) of 1,1-bis(methylthio)-2-nitroethylene.

Stirring was continued for 48 hours at room temperature and the reactionmixture was poured onto 2.5 liters of ice-water mixture.

The dark green insoluble that formed was drained on a No. 3 frit andthen washed with plenty of water, 3×200 ml of ethyl acetate and thenwith 3×200 ml of isopropyl ether.

After drying under vacuum in the presence of P₂O₅, 36.77 g of a darkgreen solid corresponding to the expected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrometry were consistent with the expected structure.

The quasi-molecular ions [M+H]⁺, [M+Na]⁺, [2M+Na]⁺ of the expectedmolecule C₁₁H₁₁N₃O₂S were mainly detected.

Synthesis of2-(methylsulphonyl)-3-nitro-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridine

267.6 g of Oxone (3 eq.), 800 ml of water and 36.17 g of2-(methylsulphanyl)-3-nitro-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridine(0.145 mol) obtained previously, were put, successively, in a 3-literthree-necked flask equipped with a mechanical stirrer and an internaltemperature sensor. The whole was stirred at room temperature.

To complete the reaction, Oxone (89.2 g, 1 eq.) was added and after 4hours with stirring at room temperature, the reaction stopped.

The solid that formed was washed with plenty of water until a filtratewas obtained that no longer contained peroxides. Then it was put undervacuum at 40° C. over P₂O₅.

35.31 g of the expected product was obtained (yellow solid).

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrometry were consistent with the expected structure.

The quasi-molecular ions [M−H]⁻, [M+H]⁺, [M+Na]⁺, [M+NA+CH₃OH]⁺,[2M+Na]⁺ of the expected molecule C₁₁H₁₁N₃O₄S were mainly detected.

Synthesis ofN,N-dimethyl-N′-(3-nitro-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridin-2-yl)ethane-1,2-diamine

50 ml of N-methylpyrrolidinone, 10 g (0.03555 mol) of2-(methylsulphonyl)-3-nitro-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridineand 7.8 ml of N,N-dimethylethylene diamine were put in a 250-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and heated at 70° C. on an oil bath for 4 hours.

The reaction mixture was cooled to room temperature and then poured ontoa mixture of 200 g of ice and water. The yellow compound that hascrystallized was drained on a frit, washed with 2×100 ml of water andthen with 3×100 ml of isopropyl ether. After drying at 35° C. undervacuum in the presence of P₂O₅, for 12 hours, 8.32 g of a green solidcorresponding to the expected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrophotometry were consistent with the expected structure. Thequasi-molecular ions of the expected molecule C₁₄H₁₉N₅O₂ were mainlydetected.

Synthesis ofN-2-[2-(dimethylamino)ethyl]-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridine-2,3-diaminedihydrochloride

150 ml of ethanol and 2 g of zinc powder were put in a 250-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and brought to reflux.

Then added dropwise were 2 ml of acid acetic and then a solution of 5 mlof water and 2 g ofN,N-dimethyl-N′-(3-nitro-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridin-2-yl)ethane-1,2-diamine.

At the end of discharge, 1 ml of acetic acid was added dropwise andreflux was maintained for 2 hours. At the end of reduction, the zinc wasremoved by filtration under argon on a bed of Celite and the filtratewas collected in a flask containing 50 ml of previously cooled 6Nhydrochloric isopropanol.

Precipitation of a greyish-blue solid was observed. This was drained ona No. 3 frit and washed with 2×15 ml of ethanol and 2×50 ml of isopropylether. After drying under vacuum in the presence of P₂O₅ and sodatablets, 1.92 g of a bluish-green powder corresponding to the expectedcompound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrophotometry were consistent with the expected structure.

The quasi-molecular ion [M+H]⁺ of the expected molecule C₁₄H₂₁N₅ wasmainly detected.

Example 262-[(3-amino-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridin-2-yl)amino]ethanolhydrochloride

Synthesis of2-[(3-nitro-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridin-2-yl)amino]ethanol

50 ml of N-methylpyrrolidinone, 10 g (0.03555 mol) of2-(methylsulphonyl)-3-nitro-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridineand 4.29 ml of ethanolamine were put in a 250-ml three-necked flaskequipped with a bulb condenser, a thermometer and a magnetic stirrer,and heated at 70° C. on an oil bath for 5 hours.

The reaction mixture was cooled to room temperature and then poured ontoa mixture of 200 g of ice and water. The yellow compound thatcrystallized was formed on a No. 3 frit, washed with water 2×100 ml andthen with 3×100 ml of isopropyl ether. After drying at 35° C. undervacuum in the presence of P₂O₅ for 12 hours, 8.70 g of a green solidcorresponding to the expected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrophotometry were consistent with the expected structure.

The quasi-molecular ions [M+H]⁺, [M+Na]⁺, [M+Na+CH₃OH]⁺, [M+Na+CH₃CN]⁺,[2M+Na]⁺, [M−H]⁻ of the expected molecule C₁₂H₁₄N₄O₃ were mainlydetected.

Synthesis of2-[(3-amino-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridin-2-yl)amino]ethanolhydrochloride

50 ml of ethanol and 2 g of zinc powder were put in a 100-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and brought to reflux.

Then added dropwise were 2 ml of acid acetic then, in portions, 1 g of2-[(3-nitro-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridin-2-yl)amino]ethanol.At the end of discharge, 1 ml of acid acetic was added dropwise andreflux was maintained for 2 hours.

At the end of reduction, the zinc was removed by filtration under argonon a bed of Celite and the filtrate was collected in a flask containing50 ml of previously cooled 6N hydrochloric isopropanol.

Precipitation of a greyish-blue solid was observed. This was drained ona No. 3 frit and then washed with 2×15 ml of ethanol and 2×50 ml ofisopropyl ether. After drying under vacuum in the presence of P₂O₅ andsoda tablets, 0.96 g of a bluish-green powder corresponding to theexpected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrophotometry were consistent with the expected structure.

The quasi-molecular ions [M+H]⁺, [M+Na]⁺, [M+H+CH₃OH]⁺, [M−H]⁻, [M+Cl]⁻of the expected molecule C₁₂H₁₆N₄O were detected.

Example 272-methoxy-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridin-3-aminehydrochloride

Synthesis of2-methoxy-3-nitro-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridine

35 ml of methanol, 10 g (0.03555 mol) of2-(methylsulphonyl)-3-nitro-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridineand 33 ml of 30% sodium methylate were put in a 250-ml three-neckedflask equipped with a bulb condenser, a thermometer and a magneticstirrer, and stirred for 18 hours.

The compound that has crystallized was drained on a frit, washed with2×25 ml of water, 10 ml of methanol and then with 3×50 ml of isopropylether. After drying at 35° C. under vacuum in the presence of P₂O₅ for12 hours, 7.82 g of a beige solid corresponding to the expected compoundwas recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrophotometry were consistent with the expected structure.

The quasi-molecular ions [M+H]⁺, [M+Na]⁺, [M+Na+CH₃OH]⁺, [2M+Na]⁺ weremainly detected.

Synthesis of2-methoxy-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridin-3-aminehydrochloride

50 ml of ethanol and 5 g of zinc powder were put in a 500-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and brought to reflux.

Then added dropwise were 5 ml of acid acetic and then, in portions, 5 gof2-methoxy-3-nitro-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridine.At the end of discharge, 1 ml of acetic acid was added dropwise andreflux was maintained for 2 hours.

At the end of reduction, the zinc was removed by filtration under argonon a bed of Celite and the filtrate was collected in a flask containing50 ml of previously cooled 6N hydrochloric isopropanol.

Precipitation of a bluish-grey solid was observed. This was drained on aNo. 3 frit and washed with 2×15 ml of ethanol and 2×50 ml of isopropylether. After drying under vacuum in the presence of P₂O₅ and sodatablets, 3.92 g of a bluish-grey powder corresponding to the expectedcompound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrophotometry were consistent with the expected structure.

The expected cation [C₁₅H₂₂N₅O₂]⁺ was mainly detected.

Example 282-isopropoxy-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridin-3-aminehydrochloride

Synthesis of2-isopropoxy-3-nitro-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridine

100 ml of THF, 10 g (0.03555 mol)2-(methylsulphonyl)-3-nitro-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridineand 7.29 g (0.08887 mol) of sodium isopropoxide, were put in portions,in a 250-ml three-necked flask equipped with a bulb condenser, athermometer and a magnetic stirrer, and stirred for 30 minutes.

The mixture was poured into 300 ml of water, and the compound thatcrystallized was drained on a No. 3 frit, washed with plenty of waterand then with 4×50 ml of isopropyl ether. After drying at 35° C. undervacuum in the presence of P₂O₅ for 12 hours, 3.70 g of a deep yellowsolid corresponding to the expected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrophotometry were consistent with the expected structure.

The quasi-molecular ions [M+H]⁺, [M+Na]⁺, [M+Na+CH₃OH]⁺, [2M+Na]⁺ weremainly detected.

Synthesis of2-isopropoxy-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridin-3-aminehydrochloride

150 ml of ethanol and 3 g of zinc powder were put in a 250-mlthree-necked flask equipped with a bulb condenser, a thermometer and amagnetic stirrer, and brought to reflux.

Then added dropwise were 2 ml of acid acetic and then, in portions, 3 gof2-isopropoxy-3-nitro-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyridine.At the end of discharge, 1 ml of acetic acid was added dropwise andreflux was maintained for 2 hours.

At the end of reduction, the zinc was removed by filtration under argonon a bed of Celite and the filtrate was collected in a flask containing50 ml of previously cooled 6N hydrochloric isopropanol.

The filtrate was concentrated to 1/3, then taken up several times inether. Slow crystallization of a light green solid was observed. Thiswas drained on a No. 3 frit and washed with 2×50 ml of ether. Afterdrying under vacuum in the presence of P₂O₅ and soda tablets, 1.67 g ofa pale pink powder corresponding to the expected compound was recovered.

NMR analyses (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and massspectrophotometry were consistent with the expected structure.

The quasi-molecular ions [M+H]⁺, [M+Na]⁺, [M+H+CH₃OH]⁺ of the expectedmolecule C₁₀H₁₃N₃O were detected.

Example 29 2-(2-piperidin-1-ylethoxy)pyrazolo[1,5-a]pyridin-3-aminechlorhydrate

General Synthesis

Synthesis of 3-nitro-2-(2-piperidin-1-ylethoxy)pyrazolo[1,5-a]pyridine

10 ml of water and 13.8 ml (0.103 mol) of N-(2-hydroxyethyl)piperidinewere put in a 250 ml three-necked flask equipped with a bulb condenser,a thermometer, and a magnetic stirrer and cooled to 0° C., then asolution containing 8.29 g (0.207 mol) of soda and ml of water was addedin 15 minutes.

The mixture was stirred at this temperature for 15 minutes, then asolution containing 100 ml of N-methylpyrrolidinone and 10 g (0.04145mol) of 2-(methylsulfonyl)-3-nitropyrazolo[1,5-a]pyridine was addeddropwise in 20 minutes.

The heterogeneous violet mixture obtained was stirred for 4 hours atambient temperature. The solid formed was drained and washed with plentyof water until a neutral pH was obtained, then with 4×50 ml of isopropylether. After drying at 35° C. under vacuum, in the presence of P₂O₅, for12 hours, 3.70 g of a beige solid corresponding to the expected compoundwas recovered.

NMR analyses (1H 400 MHz and 13C 100.61 MHz DMSO d6) and massspectrophotometry were consistent with the expected structure.

The quasi-molecular ions [M+H]⁺, [M+Na]⁺, [M+Na+CH₃OH]⁺, [2M+Na]⁺ weremainly detected.

Synthesis of 2-(2-piperidin-1-ylethoxy)pyrazolo[1,5-a]pyridin-3-aminechlorohydrate

30 ml of ethanol and 2.75 g of zinc powder were placed in a 100 mlthree-necked flask equipped with a bulb condenser, a thermometer, and amagnetic stirrer, and brought to reflux. Then 550 μl of acetic acid wasadded dropwise, and then, in portions, 2.75 g of3-nitro-2-(2-piperidin-1-ylethoxy)pyrazolo[1,5-a]pyridine. At the end ofthe addition, 2 drops of acetic acid were added and reflux wasmaintained for 4 hours.

At the end of reduction, the zinc was removed by filtration under argonon a bed of Celite and the filtrate was collected in a flask containing100 ml of previously cooled 6N hydrochloric isopropanol.

The filtrate was concentrated to 1/3 of volume, then taken up severaltimes in ether. Slow crystallization of a violet solid was observed.This was drained on a No. 3 frit and washed with a minimal amount ofisopropanol and then with 3×30 ml of ether. After drying under vacuum,in the presence of P₂O₅ and soda tablets, 1.71 g of a pale pink powdercorresponding to the expected compound were recovered.

The NMR analyses (1H 400 MHz and 13C 100.61 MHz DMSO d6) and massspectrophotometry were consistent with the expected structure.

The quasi-molecular ions [M+H]⁺, [M+Na]⁺, [M+H+CH₃OH] of the expectedmolecule C₁₄H₂ON₄O were detected.

Example 30 2-[2-(dimethylamino)ethoxy]pyrazolo[1,5-a]pyridin-3-aminechlorohydrate

General Synthesis

Synthesis ofN,N-dimethyl-2-[(3-nitropyrazolo[1,5-a]pyridin-2-yl)oxy]ethanamine

10 ml of water and 10.3 ml (0.103 mol) of N,N-dimethylethanolamine wereput in a 250 ml three-necked flask equipped with a bulb condenser, athermometer, and a magnetic stirrer and cooled to 00° C., then asolution containing 8.29 g (0.207 mol) of soda and ml of water wereadded in 15 minutes.

The solution was stirred at this temperature for 15 minutes, then asolution containing 100 ml of N-methylpyrrolidinone and 10 g (0.04145mol) of 2-(methylsulfonyl)-3-nitropyrazolo[1,5-a]pyridine is addeddropwise in 20 minutes.

The mixture obtained was light violet and was stirred for 6 hours atambient temperature. The reaction mixture was pored onto 500 ml ofwater. The beige solid formed was drained and washed with plenty ofwater until a neutral pH was obtained, then with 4×50 ml of isopropylether. After drying at 35° C. under vacuum, in the presence of P₂O₅, for12 hours, 5.01 g of a beige solid corresponding to the expected compoundwas recovered.

NMR analyses (1H 400 MHz and 13C 100.61 MHz DMSO d6) and massspectrophotometry were consistent with the expected structure.

The quasi-molecular ions [M+H]⁺, [M+Na]⁺, [M+Na+CH₃OH]⁺, [2M+Na]⁺ weremainly detected.

Synthesis of 2-[2-(dimethylamino)ethoxy]pyrazolo[1,5-a]pyridin-3-aminechlorhydrate

20 ml of ethanol and 25 of zinc powder were put in a 100 ml three-neckedflask equipped with a bulb condenser, a thermometer, and a magneticstirrer, and brought to reflux. Two drops of acetic acid were added, andthen, in portions, 2 g ofN,N-dimethyl-2-[(3-nitropyrazolo[1,5-a]pyridin-2-yl)oxy]ethanamine. Atthe end of the addition, two drops of acetic acid were added and refluxwas maintained for 17 hours.

At the end of reduction, the zinc was removed by filtration under argonon a bed of Celite and the filtrate was collected in a flask containing100 ml of previously cooled 6N hydrochloric isopropanol.

The filtrate was concentrated to 1/3 of volume, and then taken upseveral times in ether. Slow crystallization of a violet solid wasobserved. This was drained on a No. 3 frit and washed with a minimalamount of isopropanol and then with 3×30 ml of ether. After drying undervacuum, in the presence of P₂O₅ and soda tablets, 2.80 g of a paleviolet powder corresponding to the expected compound were recovered.

The NMR analyses (1H 400 MHz and 13C 100.61 MHz DMSO d6) and massspectrophotometry were consistent with the expected structure.

The quasi-molecular ions [M+H]⁺, [M+Na]⁺, [M+H+CH₃OH] of the expectedmolecule C₁₁H₁₆N₄O were detected.

Examples of Dyeing

The following dyeing compositions were prepared

2-isopropoxy- 10⁻³ 10⁻³ 10⁻³ 10⁻³ 10⁻³ 10⁻³ 10⁻³ pyrazolo[1,5- mole molemole mole mole mole mole a]pyridin-3-amine hydrochlorideBenzene-1,3-diol 10⁻³ mole 5-Amino-2-methyl- 10⁻³ phenol mole1H-Indol-6-ol 10⁻³ mole 2-Amino-pyridin-3-ol 10⁻³ mole 3,6-Dimethyl-1H-10⁻³ pyrazolo[5,1- mole c][1,2,4]triazole 2-(2,4-Diamino- 10⁻³phenoxy)-ethanol, mole hydrochloride 3-Amino-2-chloro-6- 10⁻³methyl-phenol, mole hydrochloride Dyeing support (1) (*) (*) (*) (*) (*)(*) (*) Demineralized water 100 g 100 g 100 g 100 g 100 g 100 g 100 gq.s.f. Shade observed bright bright bright bright chromatic bright redbright red chromatic red violet-red red chromatic red red 2-[3- 10⁻³mole 10⁻³ mole 10⁻³ mole 10⁻³ mole (dimethylamino)pyrrolidin-1-yl]pyrazolo[1,5-a]pyridin-3- amine hydrochloride 5-Amino-2-methyl-phenol10⁻³ mole 1H-Indol-6-ol 10⁻³ mole 3,6-Dimethyl-1H- 10⁻³ molepyrazolo[5,1- c][1,2,4]triazole 2-(2,4-Diamino-phenoxy)- 10⁻³ moleethanol, hydrochloride Dyeing support (2) (*) (*) (*) (*) Demineralizedwater q.s.f. 100 g 100 g 100 g 100 g Shade observed bright blue orange-red bright greenish- brown blue-grey 2-[3-(dimethylamino) 10⁻³ mole 10⁻³mole pyrrolidin-1-yl]pyrazolo[1,5- a]pyridin-3-amine hydrochloride5-Amino-2-methyl-phenol 10⁻³ mole 2-(2,4-Diamino-phenoxy)- 10⁻³ moleethanol, hydrochloride Dyeing support (1) (*) (*) Demineralized waterq.s.f. 100 g 100 g Shade observed blue-grey greenish- blue-grey2-methoxy-7- 10⁻³ mole 10⁻³ mole 10⁻³ mole 10⁻³ mole 10⁻³ mole 10⁻³ molemethylpyrazolo[1,5- a]pyridin-3-amine hydrochloride 5-Amino-2-methyl-10⁻³ mole phenol 1H-Indol-6-ol 10⁻³ mole 2-Amino-pyridin-3-ol 10⁻³ mole3,6-Dimethyl-1H- 10⁻³ mole pyrazolo[5,1- c][1,2,4]triazole2-(2,4-Diamino- 10⁻³ mole phenoxy)-ethanol, hydrochloride3-Amino-2-chloro-6- 10⁻³ mole methyl-phenol, hydrochloride Dyeingsupport (2) (*) (*) (*) (*) (*) (*) Demineralized water 100 g 100 g 100g 100 g 100 g 100 g q.s.f. Shade observed bright bright red reddish-bright bright red bright chromatic brown chromatic chromatic red red red2-methoxy-7- 10⁻³ mole 10⁻³ mole 10⁻³ mole 10⁻³ mole 10⁻³ mole 10⁻³ molemethylpyrazolo[1,5- a]pyridin-3-amine hydrochloride 5-Amino-2-methyl-10⁻³ mole phenol 1H-Indol-6-ol 10⁻³ mole 2-Amino-pyridin-3-ol 10⁻³ mole3,6-Dimethyl-1H- 10⁻³ mole pyrazolo[5,1- c][1,2,4]triazole2-(2,4-Diamino- 10⁻³ mole phenoxy)-ethanol, hydrochloride3-Amino-2-chloro-6- 10⁻³ mole methyl-phenol, hydrochloride Dyeingsupport (1) (*) (*) (*) (*) (*) (*) Demineralized water 100 g 100 g 100g 100 g 100 g 100 g q.s.f. Shade observed bright bright brown-red brightbright red bright chromatic reddish- chromatic chromatic red brown redred 2-pyrrolidin-1-ylpyrazolo[1,5-a]pyridin-3- 10⁻³ mole 10⁻³ mole aminehydrochloride 5-Amino-2-methyl-phenol 10⁻³ mole 2-(2,4-Diamino-phenoxy)-10⁻³ mole ethanol, hydrochloride Dyeing support (2) (*) (*)Demineralized water q.s.f. 100 g 100 g Shade observed grey-green brightgreenish- blue-grey 2-pyrrolidin-1-ylpyrazolo[1,5-a]pyridin-3- 10⁻³ mole10⁻³ mole amine hydrochloride 5-Amino-2-methyl-phenol 10⁻³ mole2-(2,4-Diamino-phenoxy)- 10⁻³ mole ethanol,hydrochloride Dyeing support(1) (*) (*) Demineralized water q.s.f. 100 g 100 g Shade observedgreenish-blue grey-greenish-blue N2-[3-(1H-imidazol- 10⁻³ mole 10⁻³ mole10⁻³ mole 10⁻³ mole 10⁻³ mole 10⁻³ mole 1-yl)propyl] pyrazolo[1,5-a]pyridine-2,3- diamine hydrochloride Benzene-1,3-diol 10⁻³ mole5-Amino-2-methyl- 10⁻³ mole phenol 1H-Indol-6-ol 10⁻³ mole3,6-Dimethyl-1H- 10⁻³ mole pyrazolo[5,1- c][1,2,4]triazole2-(2,4-Diamino- 10⁻³ mole phenoxy)-ethanol, hydrochloride3-Amino-2-chloro-6- 10⁻³ mole methyl-phenol, hydrochloride Dyeingsupport (2) (*) (*) (*) (*) (*) (*) Demineralized 100 g 100 g 100 g 100g 100 g 100 g water q.s.f. Shade observed grey- Grey- Grey- grey-greenish- greenish- green greenish- green green blue blue blueN2-[3-(1H-imidazol-1- 10⁻³ mole 10⁻³ mole 10⁻³ moleyl)propyl]pyrazolo[1,5-a]pyridine- 2,3-diamine hydrochloride5-Amino-2-methyl-phenol 10⁻³ mole 2-(2,4-Diamino-phenoxy)- 10⁻³ moleethanol, hydrochloride 3-Amino-2-chloro-6-methyl- 10⁻³ mole phenol,hydrochloride Dyeing support (1) (*) (*) (*) Demineralized water q.s.f.100 g 100 g 100 g Shade observed bluish-grey grey- greenish-blue green2-(4-methylpiperazin-1- 10⁻³ mole 10⁻³ mole 10⁻³ mole 10⁻³ moleyl)pyrazolo[1,5-a]pyridin-3- amine hydrochloride 5-Amino-2-methyl-phenol10⁻³ mole 1H-Indol-6-ol 10⁻³ mole 2-(2,4-Diamino-phenoxy)- 10⁻³ moleethanol, hydrochloride 3-Amino-2-chloro-6-methyl- 10⁻³ mole phenol,hydrochloride Dyeing support (2) (*) (*) (*) (*) Demineralized waterq.s.f. 100 g 100 g 100 g 100 g Shade observed grey-violet- orange brightbluish red greenish- grey blue grey 2-(4-methylpiperazin-1- 10⁻³ mole10⁻³ mole 10⁻³ mole yl)pyrazolo[1,5-a]pyridin-3- amine hydrochloride5-Amino-2-methyl-phenol 10⁻³ mole 2-(2,4-Diamino-phenoxy)- 10⁻³ moleethanol, hydrochloride 3-Amino-2-chloro-6-methyl- 10⁻³ mole phenol,hydrochloride Dyeing support (1) (*) (*) (*) Demineralized water q.s.f.100 g 100 g 100 g Shade observed grey-violet grey-greenish- bluish-greyblue 2-[(3-aminopyrazolo[1,5-a]pyridin-2-yl)amino]ethanol 10⁻³ molehydrochloride 2-(2,4-Diamino-phenoxy)-ethanol, hydrochloride 10⁻³ moleDyeing support (2) (*) Demineralized water q.s.f. 100 g Shade observedgrey-greenish-blue 2-[(3-aminopyrazolo[1,5-a]pyridin-2- 10⁻³ mole 10⁻³mole yl)amino]ethanol hydrochloride 2-(2,4-Diamino-phenoxy)- 10⁻³ moleethanol, hydrochloride 3-Amino-2-chloro-6-methyl- 10⁻³ mole phenol,hydrochloride Dyeing support (1) (*) (*) Demineralized water q.s.f. 100g 100 g Shade observed bright greenish-blue blue1-[(3-aminopyrazolo[1,5-a]pyridin-2-yl)amino]propan-2-ol 10⁻³ molehydrochloride 2-(2,4-Diamino-phenoxy)-ethanol, hydrochloride 10⁻³ moleDyeing support (2) (*) Demineralized water q.s.f. 100 g Shade observedgrey-green 1-[(3-aminopyrazolo[1,5-a]pyridin-2- 10⁻³ mole 10⁻³ mole 10⁻³mole yl)amino]propan-2-ol hydrochloride 5-Amino-2-methyl-phenol 10⁻³mole 2-(2,4-Diamino-phenoxy)- 10⁻³ mole ethanol, hydrochloride3-Amino-2-chloro-6-methyl- 10⁻³ mole phenol, hydrochloride Dyeingsupport (1) (*) (*) (*) Demineralized water q.s.f. 100 g 100 g 100 gShade observed bluish-grey grey-green greenish- blueN2-ethylpyrazolo[1,5-a]pyridine-2,3-diamine hydrochloride 10⁻³ mole2-(2,4-Diamino-phenoxy)-ethanol, hydrochloride 10⁻³ mole Dyeing support(2) (*) Demineralized water q.s.f. 100 g Shade observedgrey-yellow-green N2-ethylpyrazolo[1,5-a]pyridine-2,3-diaminehydrochloride 10⁻³ mole 3-Amino-2-chloro-6-methyl-phenol, hydrochloride10⁻³ mole Dyeing support (1) (*) Demineralized water q.s.f. 100 g Shadeobserved greenish-blue 2-[(3-amino-7,8-dihydro-6H- 10⁻³ mole 10⁻³ mole10⁻³ mole 10⁻³ mole cyclopenta[e]pyrazolo[1,5-a]pyridin-2-yl)amino]ethanol hydrochloride 5-Amino-2-methyl-phenol 10⁻³ mole1H-Indol-6-ol 10⁻³ mole 2-(2,4-Diamino-phenoxy)- 10⁻³ mole ethanol,hydrochloride 3-Amino-2-chloro-6-methyl- 10⁻³ mole phenol, hydrochlorideDyeing support (1) (*) (*) (*) (*) Demineralized water q.s.f. 100 g 100g 100 g 100 g Shade observed green yellow-green green greenish-blue2-[(3-amino-7,8- 10⁻³ 10⁻³ 10⁻³ 10⁻³ 10⁻³ 10⁻³ 10⁻³ dihydro-6H-cyclo-mole mole mole mole mole mole mole penta[e] pyrazolo[1,5-a]pyridin-2-yl)amino]ethanol hydrochloride Benzene-1,3-diol 10⁻³ mole5-Amino-2-methyl- 10⁻³ phenol mole 1H-Indol-6-ol 10⁻³ mole2-Amino-pyridin-3-ol 10⁻³ mole 3,6-Dimethyl-1H- 10⁻³ pyrazolo[5,1- molec][1,2,4]triazole 2-(2,4-Diamino- 10⁻³ phenoxy)-ethanol, molehydrochloride 3-Amino-2-chloro-6- 10⁻³ methyl-phenol, mole hydrochlorideDyeing support (2) (*) (*) (*) (*) (*) (*) (*) Demineralized water 100 g100 g 100 g 100 g 100 g 100 g 100 g q.s.f. Shade observed green greengrey- green green grey- green green green 2-methoxy-7,8-dihydro- 10⁻³10⁻³ 10⁻³ 10⁻³ mole 10⁻³ 10⁻³ 6H-cyclopenta[e]pyrazolo[1,5- mole molemole mole mole a]pyridin- 3-amine hydrochloride Benzene-1,3-diol 10⁻³mole 1H-Indol-6-ol 10⁻³ mole 2-Amino-pyridin-3-ol 10⁻³ mole3,6-Dimethyl-1H- 10⁻³ mole pyrazolo[5,1- c][1,2,4]triazole2-(2,4-Diamino- 10⁻³ phenoxy)-ethanol, mole hydrochloride3-Amino-2-chloro-6- 10⁻³ methyl-phenol, mole hydrochloride Dyeingsupport (1) (*) (*) (*) (*) (*) (*) Demineralized water 100 g 100 g 100g 100 g 100 g 100 g q.s.f. Shade observed bright bright grey brightbright bright reddish- reddish- chromatic reddish- red violet- grey redbrown grey 2-methoxy-7,8-dihydro- 10⁻³ 10⁻³ 10⁻³ 10⁻³ 10⁻³ 10⁻³ 10⁻³ 6H-mole mole mole mole mole mole mole cyclopenta[e]pyrazolo[1,5-a]pyridin-3-amine hydrochloride Benzene-1,3-diol 10⁻³ mole5-Amino-2-methyl- 10⁻³ phenol mole 1H-Indol-6-ol 10⁻³ mole2-Amino-pyridin-3-ol 10⁻³ mole 3,6-Dimethyl-1H- 10⁻³ pyrazolo[5,1- molec][1,2,4]triazole 2-(2,4-Diamino- 10⁻³ phenoxy)- moleethanol,hydrochloride 3-Amino-2-chloro-6- 10⁻³ methyl- mole phenol,hydrochloride Dyeing support (2) (*) (*) (*) (*) (*) (*) (*)Demineralized water 100 g 100 g 100 g 100 g 100 g 100 g 100 g q.s.f.Shade observed bright bright bright bright bright bright bright grey-red reddish- grey red reddish- red violet brown brownN2-[2-(dimethylamino)ethyl]-7,8-dihydro-6H- 10⁻³ mole 10⁻³ mole 10⁻³mole cyclopenta[e]pyrazolo[1,5-a]pyridine-2,3- diamine hydrochloride5-Amino-2-methyl-phenol 10⁻³ mole 2-(2,4-Diamino-phenoxy)- 10⁻³ moleethanol, hydrochloride 3-Amino-2-chloro-6-methyl- 10⁻³ molephenol,hydrochloride Dyeing support (1) (*) (*) (*) Demineralized waterq.s.f. 100 g 100 g 100 g Shade observed greenish- green greenish- blueblue N2-[2-(dimethyl- 10⁻³ mole 10⁻³ 10⁻³ 10⁻³ 10⁻³ 10⁻³ 10⁻³amino)ethyl]-7,8- mole mole mole mole mole mole dihydro-6H-cyclo-penta[e]pyrazolo[1,5- a]pyridine-2,3- diamine hydrochlorideBenzene-1,3-diol 10⁻³ mole 5-Amino-2-methyl- 10⁻³ phenol mole1H-Indol-6-ol 10⁻³ mole 2-Amino-pyridin-3-ol 10⁻³ mole 3,6-Dimethyl-1H-10⁻³ pyrazolo[5,1- mole c][1,2,4]triazole 2-(2,4-Diamino- 10⁻³phenoxy)-ethanol, mole hydrochloride 3-Amino-2-chloro-6- 10⁻³methyl-phenol, mole hydrochloride Dyeing support (2) (*) (*) (*) (*) (*)(*) (*) Demineralized water 100 g 100 g 100 g 100 g 100 g 100 g 100 gq.s.f. Shade observed chromatic green green chromatic greenish-greenish- bright green green blue blue greenish- blueN2-[2-(diethylamino)ethyl]pyrazolo[1,5- 10⁻³ mole 10⁻³ 10⁻³ 10⁻³ molea]pyridine-2,3- mole mole diamine hydrochloride 5-Amino-2-methyl-phenol10⁻³ mole 2-Amino-pyridin-3-ol 10⁻³ mole 2-(2,4-Diamino-phenoxy)- 10⁻³ethanol,hydrochloride mole 3-Amino-2-chloro-6-methyl- 10⁻³ mole phenol,hydrochloride Dyeing support (2) (*) (*) (*) (*) Demineralized waterq.s.f. 100 g 100 g 100 g 100 g Shade observed violet-blue grey brightbright violet- blue blue N2-[2-(diethylamino)ethyl]pyrazolo[1,5- 10⁻³mole 10⁻³ mole 10⁻³ mole 10⁻³ mole a]pyridine-2,3- diamine hydrochloride5-Amino-2-methyl-phenol 10⁻³ mole 1H-Indol-6-ol 10⁻³ mole2-(2,4-Diamino-phenoxy)- 10⁻³ mole ethanol,hydrochloride3-Amino-2-chloro-6-methyl- 10⁻³ mole phenol, hydrochloride Dyeingsupport (1) (*) (*) (*) (*) Demineralized water q.s.f. 100 g 100 g 100 g100 g Shade observed bright reddish- bright blue bright violet-bluebrown violet-blue N2-[2-(diisopropylamino)ethyl]pyrazolo[1,5- 10⁻³ 10⁻³10⁻³ 10⁻³ mole 10⁻³ mole a]pyridine-2,3- mole mole mole diaminehydrochloride 5-Amino-2-methyl-phenol 10⁻³ mole 1H-Indol-6-ol 10⁻³ mole3,6-Dimethyl-1H-pyrazolo[5,1- 10⁻³ c][1,2,4]triazole mole2-(2,4-Diamino-phenoxy)- 10⁻³ mole ethanol,hydrochloride3-Amino-2-chloro-6-methyl- 10⁻³ mole phenol, hydrochloride Dyeingsupport (2) (*) (*) (*) (*) (*) Demineralized water q.s.f. 100 g 100 g100 g 100 g 100 g Shade observed bright orange- red bright brightviolet- brown blue violet- blue blueN2-[2-(diisopropylamino)ethyl]pyrazolo[1,5- 10⁻³ 10⁻³ 10⁻³ 10⁻³ mole10⁻³ 10⁻³ mole a]pyridine-2,3- mole mole mole mole diamine hydrochlorideBenzene-1,3-diol 10⁻³ mole 5-Amino-2-methyl-phenol 10⁻³ mole1H-Indol-6-ol 10⁻³ mole 3,6-Dimethyl-1H-pyrazolo[5,1- 10⁻³ molec][1,2,4]triazole 2-(2,4-Diamino-phenoxy)- 10⁻³ ethanol,hydrochloridemole 3-Amino-2-chloro-6-methyl- 10⁻³ mole phenol, hydrochloride Dyeingsupport (1) (*) (*) (*) (*) (*) (*) Demineralized water q.s.f. 100 g 100g 100 g 100 g 100 g 100 g Shade observed brown bright bright brightbright bright violet reddish- chromatic blue chromatic brown redviolet-blue N2-(2-pyridin-3-ylethyl)pyrazolo[1,5- 10⁻³ mole 10⁻³ 10⁻³mole 10⁻³ mole a]pyridine-2,3-diamine hydrochloride mole5-Amino-2-methyl-phenol 10⁻³ mole 1H-Indol-6-ol 10⁻³ mole2-(2,4-Diamino-phenoxy)- 10⁻³ mole ethanol,hydrochloride3-Amino-2-chloro-6-methyl- 10⁻³ mole phenol, hydrochloride Dyeingsupport (2) (*) (*) (*) (*) Demineralized water q.s.f. 100 g 100 g 100 g100 g Shade observed grey yellow- bright bright blue greenish- browngreenish- blue blue N2-(2-pyridin-3- 10⁻³ mole 10⁻³ 10⁻³ 10⁻³ 10⁻³ 10⁻³mole ylethyl)pyrazolo[1,5- mole mole mole mole a]pyridine-2,3-diaminehydrochloride Benzene-1,3-diol 10⁻³ mole 5-Amino-2-methyl- 10⁻³ phenolmole 1H-Indol-6-ol 10⁻³ mole 3,6-Dimethyl-1H- 10⁻³ pyrazolo[5,1- molec][1,2,4]triazole 2-(2,4-Diamino- 10⁻³ phenoxy)-ethanol, molehydrochloride 3-Amino-2-chloro-6- 10⁻³ mole methyl-phenol, hydrochlorideDyeing support (1) (*) (*) (*) (*) (*) (*) Demineralized water 100 g 100g 100 g 100 g 100 g 100 g q.s.f. Shade observed bright bright bright redbright bright greenish- violet- reddish- blue blue blue-grey blue brownN2-(2-pyridin-4- 10⁻³ mole 10⁻³ mole 10⁻³ moleylethyl)pyrazolo[1,5-a]pyridine- 2,3-diamine hydrochloride5-Amino-2-methyl-phenol 10⁻³ mole 2-(2,4-Diamino-phenoxy)- 10⁻³ moleethanol,hydrochloride 3-Amino-2-chloro-6-methyl- 10⁻³ mole phenol,hydrochloride Dyeing support (2) (*) (*) (*) Demineralized water q.s.f.100 g 100 g 100 g Shade observed grey bright greenish- blue blueN2-(2-pyridin-4- 10⁻³ 10⁻³ mole 10⁻³ mole 10⁻³ mole 10⁻³ moleylethyl)pyrazolo[1,5- mole a]pyridine-2,3-diamine hydrochlorideBenzene-1,3-diol 10⁻³ mole 5-Amino-2-methyl- 10⁻³ mole phenol1H-Indol-6-ol 10⁻³ mole 2-(2,4-Diamino- 10⁻³ mole phenoxy)-ethanol,hydrochloride 3-Amino-2-chloro-6- 10⁻³ mole methyl-phenol, hydrochlorideDyeing support (1) (*) (*) (*) (*) (*) Demineralized water 100 g 100 g100 g 100 g 100 g q.s.f. Shade observed grey bright reddish- bright blueviolet- brown greenish- blue blue 2-isopropoxypyrazolo[1,5- 10⁻³ 10⁻³mole 10⁻³ 10⁻³ 10⁻³ 10⁻³ mole a]pyridin-3- mole mole mole mole aminehydrochloride Benzene-1,3-diol 10⁻³ mole 5-Amino-2-methyl- 10⁻³ molephenol 1H-Indol-6-ol 10⁻³ mole 2-Amino-pyridin-3-ol 10⁻³ mole2-(2,4-Diamino- 10⁻³ phenoxy)-ethanol, mole hydrochloride3-Amino-2-chloro-6- 10⁻³ mole methyl-phenol, hydrochloride Dyeingsupport (2) (*) (*) (*) (*) (*) (*) Demineralized water 100 g 100 g 100g 100 g 100 g 100 g q.s.f. Shade observed reddish- bright red red brightbright brown chromatic red chromatic red red (*): dyeing support (1) pH7 [A.S. = active substance] Ethanol, 96° 20.8 g Sodium metabisulphite,35% aqueous solution 0.23 g A.S. Pentasodium salt ofdiethylenetriamine-pentaacetic acid, 40% 0.48 g A.S. aqueous solutionC₈-C₁₀ alkyl polyglucoside, 60% aqueous solution  3.6 g A.S. Benzylalcohol  2.0 g Polyethylene glycol with 8 units of ethylene oxide  3.0 gNa₂HPO₄ 0.28 g KH₂PO₄ 0.46 g (*): dyeing support (2) pH 9.5 Ethanol, 96°20.8 g Sodium metabisulphite, 35% aqueous solution 0.23 g A.S.Pentasodium salt of diethylenetriamine-pentaacetic acid, 40% aqueous0.48 g A.S. solution C₈-C₁₀ alkyl polyglucoside, 60% aqueous solution 3.6 g A.S. Benzyl alcohol  2.0 g Polyethylene glycol with 8 units ofethylene oxide  3.0 g NH₄Cl 4.32 g Ammonia at 20% of NH₃ 2.94 g

At the moment of use, each composition was mixed with an equal weight ofhydrogen peroxide solution at 20 volumes (6 wt. %). A final pH of 7, or9.5, was obtained.

Each mixture obtained was applied to locks of grey hair at 90% white.After a waiting time of 30 minutes, the locks were rinsed, washed with astandard shampoo, rinsed again and then dried.

The results obtained are shown in the above tables.

1. A composition for dyeing keratin fibers comprising, in a mediumsuitable for dyeing, at least one oxidation dyeing base chosen from3-aminopyrazolo-[1,5-a]-pyridine derivatives of formula (I) and saltsand solvates thereof:

in which Z₁ is chosen from an oxygen atom and a group NR₆; when Z₁ isNR₆ then R₁ and R₆ can form, together with the nitrogen atom to whichthey are attached, a saturated, unsaturated or aromatic heterocycle with5 to 8 ring members, optionally substituted, Z₁ can alternatively bechosen from divalent radical S, SO, and SO₂ when R₁ is CH₃, R₁ and R₆are chosen from, independently: hydrogen, C₁-C₁₀ alkyl radicals,optionally substituted with at least one saturated, unsaturated oraromatic (hetero)cycle with 5 to 8 ring members, optionally substitutedsaturated, unsaturated or aromatic (hetero)cycles with 5 to 8 ringmembers, optionally substituted, R₂, R₃, R₄, R₅, independently, arechosen from: hydrogen, C₁-C₄ alkyl radicals, optionally substituted, R₂,R₃, R₄, R₅, can form, two by two with adjacent radicals, a saturated orunsaturated (hetero)cycle, optionally substituted, with the exception of2-methoxypyrazolo[1,5-a]pyridin-3-ylamine and2-morpholino-pyrazolo[1,5-a]pyridin-3-ylamine respectively of thefollowing formulae:


2. A composition according to claim 1, in which Z₁ is chosen from anoxygen atom, a radical NR₆ and a radical NR₆ forming a heterocycle withR₁.
 3. A composition according to claim 1, in which radical R₁ is chosenfrom an alkyl radical, an alkyl radical substituted with a hydroxy, analkyl radical substituted with an amino or (di)alkylamino radical, andan alkyl radical substituted with a nitrogen-containing heterocycle. 4.A composition according to claim 1, in which radical R₆ is chosen from ahydrogen atom, an alkyl radical, an alkyl radical substituted with ahydroxy radical, an amino radical, an alkylamino radical, a dialkylaminoradical, and an alkyl radical substituted with a nitrogen-containingheterocycle.
 5. A composition according to claim 3, in which the alkylradical has from 1 to 6 carbon atoms.
 6. A composition according toclaim 4, in which the alkyl radical has from 1 to 6 carbon atoms.
 7. Acomposition according to claim 1, in which R₆ forms, with R₁, aheterocycle with the nitrogen atom to which they are attached, saidheterocycle being chosen from substituted or unsubstituted imidazoles,piperazines, pyrrolidines, and diazepanes.
 8. A composition according toclaim 1, in which the radicals R₂, R₃, R₄ and R₅ independently arechosen from a hydrogen atom and a C₁-C₄ alkyl radical, which can besubstituted.
 9. A composition according to claim 1, in which theradicals R₄ and R₅ together form a saturated or unsaturated(hetero)cycle with 5 to 8 ring members.
 10. A composition according toclaim 9 in which R₄ and R₅ together form a cyclopentane radical.
 11. Acomposition according to claim 1, in which the compound of formula (I)is chosen from the following compounds and corresponding addition saltsor solvates:


12. A composition according to claim 11 in which the compound of formula(I) is chosen from: N2-ethylpyrazolo[1,5-a]pyridine-2,3-diaminedihydrochloride, 2-pyrrolidin-1-ylpyrazolo[1,5-a]pyridin-3-ylaminedihydrochloride,2-(3-dimethylaminopyrrolidin-1-yl)pyrazolo[1,5-a]pyridin-3-ylaminedihydrochloride, 2-imidazol-1-ylpyrazolo[1,5-a]pyridin-3-ylaminedihydrochloride, 2-ethoxypyrazolo[1,5-a]pyridin-3-ylaminedihydrochloride, 2-methoxy-7-methylpyrazolo[1,5-a]pyridin-3-ylaminehydrochloride,4-ethyl-2-methoxy-7-methylpyrazolo[1,5-a]pyridin-3-ylaminedihydrochloride,4-ethyl-7-methyl-2-pyrrolidin-1-ylpyrazolo[1,5-a]pyridin-3-ylaminedihydrochloride.
 13. A composition according to claim 1, wherein the atleast one oxidation base is present in an amount for each ranging from0.001 to 10 wt. % of the total weight of the dyeing composition.
 14. Acomposition according to claim 1, additionally comprising at least onecoupler chosen from meta-phenylenediamines, meta-aminophenols,meta-diphenols, naphthalenic couplers, heterocyclic couplers and theiraddition salts, as well as their mixtures.
 15. A composition accordingto claim 14, wherein the at least one coupler is present in an amountfor each ranging from 0.001 to 10 wt. % of the total weight of thedyeing composition.
 16. A method for dyeing keratin fibers, comprisingapplying a dyeing composition to keratin fibers in the presence of anoxidizing agent for a time sufficient to develop a desired coloration,wherein said dyeing composition comprises, in a medium suitable fordyeing, at least one oxidation dyeing base chosen from3-aminopyrazolo-[1,5-a]-pyridine derivatives of formula (I) and saltsand solvates thereof:

in which Z₁ is chosen from an oxygen atom and a group NR₆; when Z₁ isNR₆ then R₁ and R₆ can form, together with the nitrogen atom to whichthey are attached, a saturated, unsaturated or aromatic heterocycle with5 to 8 ring members, optionally substituted, Z₁ can alternatively bechosen from divalent radical S, SO, and SO₂ when R₁ is CH₃, R₁ and R₆are chosen from, independently: hydrogen, C₁-C₁₀ alkyl radicals,optionally substituted with at least one saturated, unsaturated oraromatic (hetero)cycle with 5 to 8 ring members, optionally substitutedsaturated, unsaturated or aromatic (hetero)cycles with 5 to 8 ringmembers, optionally substituted, R₂, R₃, R₄, R₅, independently, arechosen from: hydrogen, C₁-C₄ alkyl radicals, optionally substituted, R₂,R₃, R₄, R₅, can form, two by two with adjacent radicals, a saturated orunsaturated (hetero)cycle, optionally substituted, with the exception of2-methoxypyrazolo[1,5-a]pyridin-3-ylamine and2-morpholino-pyrazolo[1,5-a]pyridin-3-ylamine respectively of thefollowing formulae:


17. A method according to claim 16 in which the oxidizing agent ischosen from hydrogen peroxide, urea peroxide, alkali metal bromates,per-salts, per-acids and oxidase enzymes.
 18. A multi-compartment kit inwhich a first compartment contains a dyeing composition and a secondcompartment contains an oxidizing agent, said dyeing compositioncomprising, in a medium suitable for dyeing, at least one oxidationdyeing base chosen from 3-aminopyrazolo-[1,5-a]-pyridine derivatives offormula (I) and salts and solvates thereof:

in which Z₁ is chosen from an oxygen atom and a group NR₆; when Z₁ isNR₆ then R₁ and R₆ can form, together with the nitrogen atom to whichthey are attached, a saturated, unsaturated or aromatic heterocycle with5 to 8 ring members, optionally substituted, Z₁ can alternatively bechosen from divalent radical S, SO, and SO₂ when R₁ is CH₃, R₁ and R₆are chosen from, independently: hydrogen, C₁-C₁₀ alkyl radicals,optionally substituted with at least one saturated, unsaturated oraromatic (hetero)cycle with 5 to 8 ring members, optionally substitutedsaturated, unsaturated or aromatic (hetero)cycles with 5 to 8 ringmembers, optionally substituted, R₂, R₃, R₄, R₅, independently, arechosen from: hydrogen, C₁-C₄ alkyl radicals, optionally substituted, R₂,R₃, R₄, R₅, can form, two by two with adjacent radicals, a saturated orunsaturated (hetero)cycle, optionally substituted, with the exception of2-methoxypyrazolo[1,5-a]pyridin-3-ylamine and2-morpholino-pyrazolo[1,5-a]pyridin-3-ylamine respectively of thefollowing formulae:


19. A compound chosen from 3-aminopyrazolo-[1,5-a]-pyridine derivativesof formula (I) and salts and solvates thereof:

in which Z₁ is chosen from an oxygen atom and a group NR₆; when Z₁ isNR₆ then R₁ and R₆ can form, together with the nitrogen atom to whichthey are attached, a saturated, unsaturated or aromatic heterocycle with5 to 8 ring members, optionally substituted, Z₁ can alternatively bechosen from divalent radical S, SO, and SO₂ when R₁ is CH₃, R₁ and R₆are chosen from, independently: hydrogen, C₁-C₁₀ alkyl radicals,optionally substituted with at least one saturated, unsaturated oraromatic (hetero)cycle with 5 to 8 ring members, optionally substitutedsaturated, unsaturated or aromatic (hetero)cycles with 5 to 8 ringmembers, optionally substituted, R₂, R₃, R₄, R₅, independently, arechosen from: hydrogen, C₁-C₄ alkyl radicals, optionally substituted, R₂,R₃, R₄, R₅, can form, two by two with adjacent radicals, a saturated orunsaturated (hetero)cycle, optionally substituted, with the exception of2-methoxypyrazolo[1,5-a]pyridin-3-ylamine and2-morpholino-pyrazolo[1,5-a]pyridin-3-ylamine respectively of thefollowing formulae: